Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 5th World Congress on Virology Atlanta, USA.

Day 2 :

Keynote Forum

Ronald Moss

Ansun Biopharma,USA

Keynote: DAS181: A Novel Host Directed Approach to Prevent and Treat Virus Infections

Time : 08:00-08:25

Conference Series Virology-2015 International Conference Keynote Speaker Ronald Moss photo
Biography:

Ronald Moss, M.D. has served as the Chief Executive Officer of Ansun Biopharma, Inc. since October 2012, and before that, served as both interim CEO and Executive Vice President of Clinical Development and Medical Affairs at Ansun from 2008 to 2012. Dr. Moss has held various executive positions in the pharmaceutical industry for over 20 years and has played a pivotal role in successfully leading companies through the complexities of drug and vaccine development. Dr. Moss has been involved in drug and vaccine development of products in Infectious Disease, Allergy, Neurology, Dermatology, Oncology, Respiratory, Transplant, and Autoimmunity in both large pharmaceutical and biotechnology companies, including roles at Aventis, Immune Response, Merck, Telos and Vical. He has also authored over 70 scientific publications. Prior to joining industry, he received his M.D. degree from Chicago Medical School, completed a residency in pediatrics at SUNY Stony Brook and completed a fellowship at the National Institutes of Health. He is double boarded in Pediatrics and Allergy and Immunology. He is also a Fellow of the American Academy and American College of Allergy and Immunology.

Abstract:

Vaccines and antivirals are currently the main approaches to prevent and treat respiratory virus infections such as influenza. The recent 2009 H1N1 pandemic and the H7N9 outbreaks exemplify the unpredictable nature of influenza viruses. Particularly concerning is the documentation NAI drug resistance to particular strains of influenza. DAS181, is an investigational host directed inhaled sialidase fusion protein and has shown in vitro and in vivo activity against many subtypes and strains of influenza virus including H7N9 and H5N1. Data will be presented from preclinical and late stage clinical studies of DAS181 against influenza. Parainfluenza lower track infection results in significant morbidity and mortality in immune-suppressed transplant patients without any licensed vaccines or antiviral drugs. In addition, the drug has shown in vitro and in vivo activity against parainfluenza virus strains (PIV-1, PIV-2, PIV-3, and PIV-4) by inactivating the virus binding receptors. DAS181 has been utilized in over 80 EIND’s, and a phase 1 study of transplant patients with severe PIV infection. Interestingly, DAS181 has also shown significant in vitro activity against other viruses including EV-68, JC, and BK. The host directed approach of DAS181 contrasts with virus specific antivirals, by circumventing considerable problems related to antiviral drug resistance, and the need for prediction of strains for effective vaccines. DAS181, an investigational drug, is currently in Phase 2 clinical trials of parainfluenza infection. Preclinical and clinical data from studies with DAS181 activity against a variety of pathogenic viruses will be presented.

Conference Series Virology-2015 International Conference Keynote Speaker Angel S. Galabov photo
Biography:

Dr. Angel Simeonov Galabov is a professor of virology in The Stephan Angeloff Institute of Microbiology, Sofia, Bulgaria. He completed his Ph.D. at Bulgarian Academy of Sciences and M.D at Higher Medical School, Sofia, Bulgaria. He held many positions in his carrier. He is Regular Member of the Bulgarian Academy of Sciences and is a member of several other Scientific Organizations. He has 40 patent inventions and 235 scientific refereed publications, including a monograph and chapters in books. He received award and honors; Awarded by the Bulgarian Academy of Sciences by the Sign of Honor “Marin Drinov” in 2009.

Abstract:

Human enteroviruses distributed worldwide are causative agents of a broad spectrum of diseases with extremely high morbidity, including a series of severe illnesses of the central nervous system, heart, endocrine pancreas, skeleton muscles, etc., as well as the common cold contributing to the development of chronic respiratory diseases, and the chronic obstructive pulmonary disease. The above diseases along with significantly high morbidity and mortality in children, in the high-risk populations (immunodeficiencies, neonates) definitely formulate the chemotherapy as the main tool for the control of enterovirus infections. At present, clinically effective antivirals for use in the treatment of enteroviral infection do not exist, in spite of the lots of work carried out in this field. The main reason for this is the development of drug resistance. . We studied the process of development of resistance to the strongest inhibitors of enteroviruses, WIN compounds (VP1 protein hydrophobic pocket blockers), especially in the models in vivo, CVB infections in mice. We introduced the tracing of a panel of phenotypic markers (MIC50 value, plaque shape and size, stability at 50o C, pathogenicity in mice) for characterization the drug-mutants (resistant and dependent) as a very important stage in the study of enterovirus inhibitors. Moreover, as a result of VP1 RNA sequence analysis performed on the model of disoxaril mutants of CVB1, we determined the molecular basis of the drug-resistance. rnThe monotherapy courses were the only approach used till now. For the first time in the research for anti-enterovirus antivirals our team introduced the testing of combination effect of the selective inhibitors of enterovirus replication with different mode of action resulting in the selection of a number of very effective in vitro double combinations revealing synergistic character of the combination effect and a broad spectrum of sensitive enteroviruses. The most prospective attainment in our study in this field was the development of a novel scheme for the combined application of anti-enteroviral substances in coxsackievirus B1 and B3 neuroinfections in newborn mice. It consisted of a consecutive, alternating and non-simultaneous, administration of the substances in the combination. The triple combinations disoxaril/guanidine/oxoglaucine (DGO), pleconaril/guanidine/oxoglaucine (PGO) and pleconaril/MDL-860/oxoglaucine (PMO) showed a high effectiveness expressed in a marked reduction of mortality rate in infected mice as compared both to the placebo group, and to the partner compounds used alone every day, and to the same combination applied simultaneously every day. Studies of the drug sensitivity of viral brain isolates from mice, treated with these combination showed not only preserved, but even increased sensitivity to the drugs included in the combination. Obviously, the consecutive alternating administration of anti-enteroviral substances hinders the occurrence of drug-resistance in the course of the experimental enteroviral infections in mice. rn

Keynote Forum

Sita Awasthi

University of Pennsylvania,USA

Keynote: Immunogenicity evaluation of a subunit vaccine for genital herpes in Rhesus macaques

Time : 08:25-08:50

Conference Series Virology-2015 International Conference Keynote Speaker Sita Awasthi photo
Biography:

Sita Awasthi has received her Ph.D in Biochemistry from Devi Ahilya University at Indore, India and her postdoctoral training from University of Pennsylvania at Philadelphia. Currently she is a Research Assistant Professor at University of Pennsylvania, Pearlman School of Medicine, Infectious Disease Division. Her research interests are HSV-2 vaccine development against genital herpes disease and HSV-2 HIV-2 co-infections. She has published numerous research articles and serving as an editorial board member of Journals of antivirals and anti retrovirals, Journal of Immunoassay and Immunochemistry.

Abstract:

About 500 million people are infected with Herpes Simplex Virus type 2 (HSV-2) worldwide. Genital HSV-2 infection is one of the major causes of genital ulcer disease and the risk of HIV-1 acquisition and transmission by 3-4 fold in humans. Efforts to prevent genital ulcer disease with acyclovir failed to reduce HIV-1 acquisition or transmission, supporting the need for an effective vaccine. We developed a trivalent gC2/gD2/gE2 (HSV-2 glycoprotein C, D and E) subunit vaccine that generates high levels of neutralizing antibodies, blocks HSV-2 immune evasion from complement, blocks IgG-Fc binding to the HSV-2 IgG Fc receptor, and is highly efficacious in preventing genital disease and viral shedding in guinea pigs. Here we present an immunogenicity evaluation of gC2/gD2/gE2 vaccine in macaques. Female macaques were immunized three times four weeks apart with 20g of each gC2, gD2, and gE2 glycoprotein or 20g gC2 alone with CpG and alum as adjuvants. After the third immunization, plasma analysis showed high titer antibody responses to each antigen, high titer neutralizing antibodies, and antibodies that blocked complement C3b binding to gC2 and IgG Fc binding to gE2. Six months after the third vaccination, the immune responses to each glycoprotein had declined 2-3 fold, but boosted within 2-weeks after a booster immunization administered at 9 months. Additionally we detected antigen specific antibody response in vaginal fluid. Importantly, analysis of PBMCs from macaques that were immunized with gC2 alone, showed a gC2 specific CD8 T cell response after 3 immunizations. In addition, antigen specific poly-functional CD4 T cell responses are induced in the trivalent vaccine group. Our results show that the trivalent gC2/gD2/gE2 subunit antigen vaccine generates highly potent immune responses in Rhesus macaques and may prove to be a promising genital herpes vaccine candidate for future trials in human.

  • Therapeutic Approaches and Targets for Viral Infections
Speaker

Chair

Sang-Moo Kang

Georgia State University,USA

Speaker

Co-Chair

Khaled Barakat

University of Alberta,Canada

Session Introduction

Ronald Moss

Ansun Biopharma,USA

Title: DAS181: A Novel Host Directed Approach to Prevent and Treat Virus Infections

Time : 08:00-08:25

Speaker
Biography:

Ronald Moss, M.D. has served as the Chief Executive Officer of Ansun Biopharma, Inc. since October 2012, and before that, served as both interim CEO and Executive Vice President of Clinical Development and Medical Affairs at Ansun from 2008 to 2012. Dr. Moss has held various executive positions in the pharmaceutical industry for over 20 years and has played a pivotal role in successfully leading companies through the complexities of drug and vaccine development. Dr. Moss has been involved in drug and vaccine development of products in Infectious Disease, Allergy, Neurology, Dermatology, Oncology, Respiratory, Transplant, and Autoimmunity in both large pharmaceutical and biotechnology companies, including roles at Aventis, Immune Response, Merck, Telos and Vical. He has also authored over 70 scientific publications. Prior to joining industry, he received his M.D. degree from Chicago Medical School, completed a residency in pediatrics at SUNY Stony Brook and completed a fellowship at the National Institutes of Health. He is double boarded in Pediatrics and Allergy and Immunology. He is also a Fellow of the American Academy and American College of Allergy and Immunology.

Abstract:

Vaccines and antivirals are currently the main approaches to prevent and treat respiratory virus infections such as influenza. The recent 2009 H1N1 pandemic and the H7N9 outbreaks exemplify the unpredictable nature of influenza viruses. Particularly concerning is the documentation NAI drug resistance to particular strains of influenza. DAS181, is an investigational host directed inhaled sialidase fusion protein and has shown in vitro and in vivo activity against many subtypes and strains of influenza virus including H7N9 and H5N1. Data will be presented from preclinical and late stage clinical studies of DAS181 against influenza. Parainfluenza lower track infection results in significant morbidity and mortality in immune-suppressed transplant patients without any licensed vaccines or antiviral drugs. In addition, the drug has shown in vitro and in vivo activity against parainfluenza virus strains (PIV-1, PIV-2, PIV-3, and PIV-4) by inactivating the virus binding receptors. DAS181 has been utilized in over 80 EIND’s, and a phase 1 study of transplant patients with severe PIV infection. Interestingly, DAS181 has also shown significant in vitro activity against other viruses including EV-68, JC, and BK. The host directed approach of DAS181 contrasts with virus specific antivirals, by circumventing considerable problems related to antiviral drug resistance, and the need for prediction of strains for effective vaccines. DAS181, an investigational drug, is currently in Phase 2 clinical trials of parainfluenza infection. Preclinical and clinical data from studies with DAS181 activity against a variety of pathogenic viruses will be presented.

Speaker
Biography:

Dr. Kang has completed his PhD in 1998 from the University of Alabama at Birmingham, and postdoctoral studies from Emory University School of Medicine. He is the professor at the Institute for Biomedical Sciences, Georgia State University. He has published more than 120 papers in reputed journals in the fields on novel viral vaccines, and immunology of vaccines and adjuvants.

Abstract:

Respiratory syncytial virus (RSV) is one of the most important causes for viral lower respiratory tract disease in humans. There is no licensed RSV vaccine. Here, we generated recombinant influenza viruses carrying the chimeric constructs of hemagglutinin (HA) and central conserved-domains of the RSV G protein or RSV F neutralizing epitopes. Chimeric recombinant influenza viruses showed lower pathogenicity without compromising immunogenicity in mice. Single intranasal inoculation of mice induced RSV neutralizing activity. Mice with single intranasal inoculation of chimeric recombinant influenza viruses were protected against RSV infection as evidenced by significant reduction of lung viral loads upon RSV challenge. Chimeric recombinant influenza virus inoculation of mice did not induce pulmonary eosinophilia and inflammation upon RSV infection. To improve cross protection overcoming HA specific immunity, we engineered replication-competent influenza A virus to express tandem repeat of heterologous M2 extracellular (M2e) domains in a chimeric HA conjugate form. Immune sera from mice with inoculation of live recombinant influenza virus expressing M2e4x-HA were effective in conferring cross protection against H1, H3, and H5 subtype influenza viruses. These findings support a concept that chimeric recombinant influenza viruses carrying the RSV neutralizing or influenza conserved-domain can be developed into new viral vaccines against RSV or influenza virus.

Rebecca D Parr

Stephen F Austin State University,USA

Title: A new antiviral therapeutic strategy for the prevention of rotavirus infections

Time : 09:10 - 09:50

Speaker
Biography:

Dr. Rebecca Parr earned her Ph.D. at Texas A&M University in College Station, TX by characterizing and comparing the spike proteins of two pathotypes of the avian coronavirus, infectious bronchitis virus. Her post-doctoral research experiences are extensive in exploring host-pathogen interactions, viral pathogenesis, and host cell protein interactions that effect cell processes of coronaviruses, baculoviruses and rotaviruses. Her recent research efforts have focused on understanding the mechanisms of action of the rotavirus enterotoxic protein, NSP4 to help design a more effective vaccine. After initiating and directing a Master of Science in Biotechnology Program at Arkansas State University, Jonesboro, AR, Dr. Parr accepted an assistant professorship at Stephen F Austin State University, Nacogdoches, TX, to continue teaching and expanding her research on antiviral strategies using natural products. She has published more than 20 papers in peer reviewed and 2 book chapters.

Abstract:

Rotaviruses (RV) are one of the leading causes of severe diarrhea in young children throughout the world. According to the WHO, rehydration, zinc supplements, nutrient-rich foods, and the availability of health professionals are key measures to treat diarrhea, but there is poor availability of interventions in developing countries. Three vaccines are available, but they only reduce the viral load, lessoning symptoms while the virus still replicates. Therefore, the search for a cost-effective therapeutic is important in reducing morbidity and mortality of RV infections in developing countries. The purpose of our studies is to investigate the effects of highly purified small molecules extracted from peanut (Arachis hypogaea) hairy root cultures. The desired effects include prevention of diarrheal symptoms and the establishment of a robust protective immunity. Recent studies show that selected natural products and synthetic small molecules inhibit specific viruses, bacteria and parasites. Stilbenoids are small molecules composed of polyphenolic compounds functioning as phytoalexins which are secondary metabolites with antimicrobial activity. They are produced by grapes, peanuts and some berries. The stilbenoid resveratrol demonstrates strong antioxidant and chemo-preventive properties. Our laboratory tested four highly purified stilbenoids to determine their effects on the RV replication in a human intestinal cell line. Our data shows a significant decrease in the amount of virus progeny with the addition of two of the four stilbenoids tested. A possible explanation of the observed effects is due to the ability of the stilbenoids to bind to cellular receptors present on the cell lines used in this study.

Khaled Barakat

University of Alberta,Canada

Title: Rational Design Of Immune Checkpoints’ Small Molecule Inhibitors

Time : 09:30 - 09:50

Speaker
Biography:

Dr. Barakat is an Assistant Professor at the school of Pharmacy at the University of Alberta, Canada. His research stands at the multidisciplinary interface of physics, biology and computer science. Dr. Barakat’s major focus is on developing and applying state-of-the-art computational drug discovery tools to discover new antiviral and immunotherapeutic drugs. Dr. Barakat has made great contributions in understanding the nature and biophysical processes underlying protein–drug, protein–protein and drug off-target interactions and predicting drug-mediated toxicity. He also received numerous awards including the CIHR and AIHS postdoctoral fellowships, the prestigious University of Alberta dissertation award and many distinction awards throughout his undergraduate and graduate studies. Dr. Barakat is also the editor of the Journal of Pharmaceutical Care & Health Systems and serves as a guest reviewer for several journals.

Abstract:

T lymphocytes preserve the immunological balance between defending against viral infection and preventing continual activated immune responses. While T cells’ specificity against cancer or viral infection is determined by the interaction between the T-cell receptor complex (TCR) and antigenic peptides bound in surface major histocompatibility complex (MHC) molecules, the full activation of T cells requires a second signal obtained by the binding of the co-receptor CD28 on T cells to CD80/86 molecules on activated antigen presenting cells (APCs). Once mobilized, T cells also express other receptors that inhibit their proliferation and cytokine production, known as immune checkpoints. Among these receptors are Cytotoxic T Lymphocyte Antigen-4 (CTLA-4), programmed death-1 (PD-1) and T cell immunoglobulin mucin-3 (TIM-3) and many others. Blocking the interactions between these receptors and their ligands emerged as a ‘game changer’ in immunotherapy, with antibodies directed toward PD-1, for example, being selected as ‘drug of the year’ for 2013 by Science. More importantly, combination blockage of multiple co-inhibitory pathways has a greater efficacy by preventing accumulation of the unblocked negative co-receptor, allowing T cells to continue to survive, proliferate, and carry out effector functions within infected cells. This talk will focus on PD-1 and will describe for the first time two accurate models for human PD-1 bound to its two human ligands. The talk will also demonstrate how these two models are being used to rationally design small molecule inhibitors for the Pd-1 pathway.

Speaker
Biography:

Dr. Wagstaff completed her Ph.D in 2007 at Monash University (Melbourne) where she has remained for her post-doctoral studies. She is presently an ARC Australian Post-Doctoral Research Fellow and manages a small research group. Her research focuses on the transport of proteins into and out of the eukaryotic cell nucleus and its therapeutic applications, including the development of inhibitors of this process as anti-viral agents and how the nuclear transport machinery may be exploited for drug delivery. She has >30 peer-reviewed publications in eminent journals (H-factor of 16) and numerous prestigious awards/prizes.

Abstract:

New World Alphaviruses, such as Eastern, Venezuelan, and Western Equine Encephalitis Viruses (EEEV, VEEV, and WEEV), cause high mortality and morbidity in equines and humans and are characterized by a febrile illness that may progress into encephalitis. The Centers for Disease Control and Prevention considers all three viruses Category B agents due to their ease of weaponization and the lack of licensed vaccines or therapeutics. The VEEV structural capsid protein blocks nuclear import in mammalian cells, most likely by forming a trimeric complex with the host nuclear import (importin 1) and export (CRM1) machinery. This complex sits inside the nuclear pore comples, the only transit for protein movement between cytoplasm and nucleus and prevents host protein movement, thus inhibiting the host anti-viral response. possibly due to its complexing with the host CRM1 and importin α/β1 nuclear transport proteins. Inhibition of viral protein nuclear transport is a rapidly growing area of investigation and hence nuclear transport inhibitors were investigated for their effectcs on Capsid. Utilising numerous transport inhibitors and a combination of in vitro protein binding assays with advanced quantitative confocal microscopy of transfected and infected cells as well as viral replication assays we demonstrate that VEEV capsid nuclear transport is a viable target for therapeutic intervention, resulting in reduced viral replication. Similarly other New World alphaviruses are also susceptible to these compounds suggesting for the first timethat a pan-antiviral therapeutic may be possible.

Speaker
Biography:

Avong is a public health pharmacist, implementing the United States Emergency Plan for AIDS Relief and the Global Fund Round 9 grants, under the Institute of Human Virology, Nigeria (IHVN). He holds a Bachelor of Pharmacy (B. Pharm) from the Ahmadu Bello University, Zaria, Nigeria and a Master of Public Health (MPH) from the University of the Western Cape, South Africa. He is also pursuing a PhD in Pharmacovigilance and Pharmaco-epidemiology. He inspired the setting- up of the spontaneous reporting system (SRS) in the HIV/AIDS and MDRTB public health programs for the detection, monitoring, treatment and reporting of adverse drug reactions (ADRs) of anti-retroviral and second line anti-tuberculosis drugs. He has supervised the collection and analysis of over 2000 individual case safety reports (ICSRs) from the HIV/AIDS and MDRTB programs and published several papers in the areas of pharmacovigilance, adherence to anti-retroviral therapy (ART) and procurement and supply management (PSM) as well as reviewed manuscripts for several notable journals. He also participated in the development of the current Nigerian “Integrated National Guidelines for HIV Prevention Treatment and Care in Nigeria”. As the head of the Pharmacy Division and Associate Director with the IHVN, he oversees the delivery of pharmaceutical care services in all the grants awarded to the IHVN. He served as the liaison officer between the Alpha Pharmacy and Stores Limited and the Federal Government of Nigeria for the importation of Narcotics for the public sector in 2003 through 2005. His current interest is promoting adherence to medications and pharmacovigilance in public health programs.

Abstract:

Background There are mixed reports on the effectiveness of fixed-dose combination (FDC) anti-retroviral medications at enhancing adherence to medications. However, some countries have completely replaced the single-drug combinations (SDCs) antiretroviral medications with the FDC, which limit treatment options and promote poly-pharmacy with attendance drug-drug interactions and additive toxicities. We investigated whether the FDCs have superior adherence effects and virologic suppression over the SDCs, to warrant their exclusive retention in anti-retroviral therapy (ART) formularies. Methods We included 501 HIV/AIDS patients (≥18 years), prescribed FDCs and SDCs at the University of Abuja Teaching Hospital, Nigeria, over a five year period (from April 2005 to May 2010). The FDCs contained three drugs with a daily pill burden of two pills while the SDCs contained a combination of single drugs and dual fixed dose combinations with daily pill burden of eight pills. Self-reported adherence to ART was defined as taking at least 95% of medication in correct doses, frequency and schedule of administration over the previous three days. Virologic suppression was defined as achieving a HIV-1 RNA of 400 copies/mL. Propensity score method was used to make sure treatments were randomly assigned in the two cohorts and logistic regression applied to compare rates of adherence to ART and virologic suppression across the two cohorts. Results: 501 patients were prescribed either FDC [206(41.2%)] or SDC [295(58.8%)]; majority of the females compared with males were FDC users [123(48.4%) vs 83(33.6%); p <0.001)]. Most of SDC users had secondary education [105(60.4%) vs 69(39.6%)], were married [181(59.9%) vs 121(40.1%)] and had informal employment [174(61.3% vs 110 (38.7%) compared with the FDC users. Most of the FDCs users were on therapy for more than 48months [127(64.5%) vs 70(35.5%] and a fewer proportion experienced adverse drug reactions [39 (44.8%) vs 48 (55.2%)] compared with the SDC users. The proportion of SDC users who achieved virologic suppression [238(80.7%) vs 164(79.6%)] or who were adherent to ART over the previous three days [259(87.8%) vs 187(90.8%)] were similar when compared to the FDC users. In a multivariate logistic regression model adjusting for age, gender, education and duration on ART, viral suppression and adherence to ART over the previous 3 days were not statistically different between the SDC and FDC users [Viral suppression (OR=0.94 (95% CI 0.54 – 1.45; p=0.64); Adherence to ART (OR=1.37 (95% CI 0.76 – 2.46; p=0.30)] . Conclusion: FDCs had no superior adherence and virologic suppression potential over the single drug combinations in this cohort. SDCs should be retained alongside the FDCs in resource limited settings.

Speaker
Biography:

Dr. Angel Simeonov Galabov is a professor of virology in The Stephan Angeloff Institute of Microbiology, Sofia, Bulgaria. He completed his Ph.D. at Bulgarian Academy of Sciences and M.D at Higher Medical School, Sofia, Bulgaria. He held many positions in his carrier. He is Regular Member of the Bulgarian Academy of Sciences and is a member of several other Scientific Organizations. He has 40 patent inventions and 235 scientific refereed publications, including a monograph and chapters in books. He received award and honors; Awarded by the Bulgarian Academy of Sciences by the Sign of Honor “Marin Drinov” in 2009. Dr. Angel Simeonov Galabov's research interests include Antiviral Substances, Biological response modifiers, Replication cycle of picorna, Papillomaviruses in cervical cancer etiology, Oncolytic parvoviruses, Population genetics, Genetic status of ancient Bulgarians (Proto-Bulgarians) and Thracians (mtDNA analysis of anthropo-archeological skeletal remains).

Abstract:

Human enteroviruses distributed worldwide are causative agents of a broad spectrum of diseases with extremely high morbidity, including a series of severe illnesses of the central nervous system, heart, endocrine pancreas, skeleton muscles, etc., as well as the common cold contributing to the development of chronic respiratory diseases, and the chronic obstructive pulmonary disease. The above diseases along with significantly high morbidity and mortality in children, in the high-risk populations (immunodeficiencies, neonates) definitely formulate the chemotherapy as the main tool for the control of enterovirus infections. At present, clinically effective antivirals for use in the treatment of enteroviral infection do not exist, in spite of the lots of work carried out in this field. The main reason for this is the development of drug resistance. . We studied the process of development of resistance to the strongest inhibitors of enteroviruses, WIN compounds (VP1 protein hydrophobic pocket blockers), especially in the models in vivo, CVB infections in mice. We introduced the tracing of a panel of phenotypic markers (MIC50 value, plaque shape and size, stability at 50o C, pathogenicity in mice) for characterization the drug-mutants (resistant and dependent) as a very important stage in the study of enterovirus inhibitors. Moreover, as a result of VP1 RNA sequence analysis performed on the model of disoxaril mutants of CVB1, we determined the molecular basis of the drug-resistance. The monotherapy courses were the only approach used till now. For the first time in the research for anti-enterovirus antivirals our team introduced the testing of combination effect of the selective inhibitors of enterovirus replication with different mode of action resulting in the selection of a number of very effective in vitro double combinations revealing synergistic character of the combination effect and a broad spectrum of sensitive enteroviruses. The most prospective attainment in our study in this field was the development of a novel scheme for the combined application of anti-enteroviral substances in coxsackievirus B1 and B3 neuroinfections in newborn mice. It consisted of a consecutive, alternating and non-simultaneous, administration of the substances in the combination. The triple combinations disoxaril/guanidine/oxoglaucine (DGO), pleconaril/guanidine/oxoglaucine (PGO) and pleconaril/MDL-860/oxoglaucine (PMO) showed a high effectiveness expressed in a marked reduction of mortality rate in infected mice as compared both to the placebo group, and to the partner compounds used alone every day, and to the same combination applied simultaneously every day. Studies of the drug sensitivity of viral brain isolates from mice, treated with these combination showed not only preserved, but even increased sensitivity to the drugs included in the combination. Obviously, the consecutive alternating administration of anti-enteroviral substances hinders the occurrence of drug-resistance in the course of the experimental enteroviral infections in mice.

Speaker
Biography:

Dr. Patricia Araujo received her Ph.D. from the University of Cambridge (UK) and was a post-doctoral fellow in the Molecular Virology Department at the Federal São Paulo University (Brasil). She is now an Chief of Virology and Serologic screen laboratories at the Blood Bank- Colsan of Federal São Paulo University.She has a long standing interest in the molecular biololgy of hepatitis B virus, mechanisms of virus replication and virus host cells interactions that result in innate immune responses to infection.

Abstract:

In a previous study, we observed that killer cell immunoglobulin-like receptors (KIR)/ Human leukocyte antigen (HLA) interactions contributed to protection or susceptibility to hepatitis B virus (HBV) infection, among blood donors with occult HBV infection (OBI) and spontaneous HBV clearance (SHC). In this context, to investigate the HLA pattern in OBI and SHC in blood donors with reactivity isolated to anti-HBc were analyzed 20 OBI cases and 40 SHC and both immune response. All samples were tested for HBsAg and anti-HBc using Chemiluminescence Immunoassay (Abbott). The immune response was previously available by NK activity, HBcAg-T-cell response, cytokine production, Treg and PD-1 expression in both groups (OBI and SHC). HLA-A, B, C, DP, DQ and DR genotyping was performed using a Luminex Multi-analyte profiling system (One Lambda, Inc., Canoga Park, CA) with the LABType SSO OneLambda typing kit (One Lambda, Inc., Canoga Park, CA).Susceptibility to HBV infection (OBI) was associated with A33(P =0.001, odds ratio [OR] = 2.42); B7(P < .001, OR = 3.97) and B15(P < .0001, OR = 2.97); DRB1*03(P < .001, OR = 3.47) and *07(P < .0001, OR = 2.34); DPB1*0901(P < .001, OR = 5.75) and HLA-C2(P < .0001, OR = 2.56). HLA-A33, B15, DRB1*07 and HLA-C1 was associated with weak immune response (P<0.0001) observed in OBI. Protection to HBV (SHC) was associated with A*0301(P <.001, OR = 4.38); B*13 0101(P <.001, OR = 4.35), DR1(P <.001, OR = 4.18); DR4(P <.001, OR = 3.67) and DR13(P <.001, OR = 3.17); DPB1*0201(P <.0001, OR = 2.36); DQA1*0301(P <.0001, OR = 2.54) and HLA-C2(P < .0001, OR = 2,14). DPB1*0201, DQA1*0301and HLA-C1 was associated with strong immune response (P<0.0001) observed in SHC. The present findings will serve as a base for subsequent functional studies into HLA molecules and viral factors in order to understand the pathogenesis of HBV infection and the relation with protection or susceptibility in hepatitis B virus (HBV) infection

Speaker
Biography:

Shaheen has completed his PhD at the age of 31 years from Al-Azhar University in applied virology. Shaheen has more than 8 years’ experience in the field of virology. Shaheen published more than 9 papers in peer-reviewed journals. Most of them, Shaheen is the first and corresponding authors. In addition to there are five manuscripts in preparation as first author evolved from PhD dissertation.

Abstract:

Coxsackie virus B3 (CVB3) represents current major threats to public health and considers as an important viral pathogen related to viral myocarditis. We determined the antiviral properties of five extracts of cassia alata leaves in vitro. The most potent extract was selected to be tested in vivo. In vitro, the cytotoxicity effect of the extracts on GMK cells was conducted by MTT colorimetric assay. The antiviral activity of the extracts was determined in three different ways (virucidal, pre-treatment, and post-treatment) by MTT and 50% tissue culture infectious dose (TCID50) methods. In vivo, after toxicity determination, the antiviral activity of the selected extract using two safe doses was evaluated based on determination of the morbidity, mortality, heart to body weight ratio (HW/BW), activities LDH, AST, and CK enzymes, virus titers, and necrosis in heart tissues in infected mice with CVB3. Our results demonstrated that the all extracts of C. alata showed antiviral activity against CVB3 in vitro with TI ranged from 0.2 to 12.2 and reduction in virus titers ranged from 0 log10 to 2.5 log10 where the methanolic extract was the most effective against CVB3 infection in vitro. In vivo, the methanol extract was found to be safe at 100 mg/kg body weight and therefor for antiviral evaluation we used 100 and 50 mg/kg body weight as safe doses. Our results suggested that the methaolic extract of C. alta was significantly reduced the morbidity, mortality, HW/BW, virus titers, necrosis and mononuclear cell infiltration of heart tissues at the both dosages. Also the extract showed the ability to maintain levels of LDH, AST, and CK enzymes at normal level in the treated infected mice compared with those untreated infected mice. This result suggested that the methaolic extract of C. alata may represent a potential antiviral agent to treatment CVB3 myocarditis.

  • Veterinary Virology
Speaker
Biography:

Professor Qian Yang has completed his PhD from College of Veterinary Medicine in Nanjing Agricultural University. She works in Shandong Agricultural University as a teacher in department of veterinary and husbandry from 1982 to 1984. Then she worded in Animal Quarantine Institute of Agricultural Ministry as an assistant researcher from 1987 to 1991. Now she works in the department of animal medical college of Nanjing agricultural university. She has published more than 50 papers in reputed journals.

Abstract:

Transmissible gastroenteritis virus (TGEV), a coronavirus, causes severe diarrhea and high mortality in newborn piglets. Porcine intestinal epithelium is the target of TGEV infection, but the mechanisms by which TGEV disrupts the actin cytoskeleton and invades the host epithelium remain largely unknown. In this study, we found that TGEV infection causes F-actin to gather at the cell membrane, and disruption of F-actin inhibits the TGEV entry into IPEC-J2 cells. The actin depolymerizing factor cofilin is critical for actin reorganization and its activity affects TGEV entry. The TGEV spike protein interacts with epidermal growth receptor (EGFR), activating the downstream phosphoinositide-3 kinase (PI3K)-serine/threonine kinase (Akt) signaling pathway, in turn causing the phosphorylation of cofilin and F-actin polymerization via Rac1/Cdc42 GTPases. EGFR is also the upstream regulator of mitogen-activated protein kinase (MAPK) signaling pathways that regulate F-actin. Our research shows that inhibition of EGFR and PI3K inhibits the entry of TGEV and confirms that EGFR is a receptor for TGEV entry. Additionally, lipid rafts act as signal platforms for the EGFR-associated signaling cascade and affect the adhesion of TGEV. Taken together, these results provide valuable insight into the mechanisms responsible for TGEV pathogenesis and may lead to the development of new methods for controlling TGEV

Maged Gomaa Hemida

King Faisal University, Saudi Arabia

Title: Dromedary camels and the transmission of MERS coronavirus (MERS-CoV)

Time : 11:10 - 11:30

Speaker
Biography:

Dr. Hemida received his Ph.D from University of Guelph, 2009. He pursued his PDF training at the the University of British Columbia (James Hogg iCapture Centre). His research area of interest is “One Health Concept” with special emphasis on emerging viruses/host interaction. Currently, studying the molecular evolution and pathogenesis of MERSCoV in the Middle East. He published more than 40 original Research papers on high impacted journals. Meanwhile, he received several Research grants, prestigious honors and scholarship throughout his academic carrier. Currently, he is a reviewer of many granting agencies as well as editorial board member of many international journals.

Abstract:

Middle East Severe Acute Coronavirus (MERS-CoV) is an existential threat to global public health. The virus has been repeatedly detected in dromedary camels (Camelus dromedaries). Adult animals in many countries in the Middle East as well as in North and East Africa have high (>90%) sero-prevalence to the virus and dromedaries are a natural host for this virus. MERS-CoV isolated from dromedaries is genetically and phenotypically similar to viruses from humans. Our goal is to summarise relevant aspects of dromedary camel husbandry, animal movements, trade and the use and consumption of camel dairy and meat products in the Middle East that may be relevant to the ecology and epidemiology of MERS. It is important to understand the ecology and epidemiology of MERS so that zoonotic disease can be prevented and epidemic or pandemic threats mitigated. To understand the modes and risk factors of human MERS, it is important to exclude cases that have been acquired from other humans or affected health care facilities and to focus on index cases of the disease. Such cases are presumed to be zoonotic in origin and livestock exposure has been reported in some, but not all or even most cases. In conclusion, transmission of MERSCoV is complicated and further studies are undergoing to explore this to improve our understanding of the role of the dromedary as a source of human infection.

Sharad Kumar Yadav

Uttar Pradesh Pandit Deen Dayal Upadhayay Pashu Chikitsa Vigyan Vishvidhyalaya Ewam Go-Anusandhan Sansthan ,India

Title: 13-2- Bovine Herpes Virus-1 (BHV-1): Current Scenario of South and East Asia

Time : 11:30 - 11:50

Speaker
Biography:

Dr Sharad Kumar Yadav has 25 years of teaching and research experience and has served to various senior positions of the University including Registrar of the DUVASU University. He is currently Professor, Head of Department of Veterinary Microbiology, at DUVASU, Mathura India. He has published number of papers in reputed International & National journals and has a vast experience in the arena of BHV-I virus

Abstract:

Bovine herpesvirus 1 (BoHV-1) is accountable for infectious bovine rhinotracheitis (IBR), a disease of major economic thrashing in the cattle industry globally. BHV-1 is a member of the genus Varicellovirus in the sub family Alphaherpesvirinae, belonging to the family Herpesviridae. The property of establishing a latent state in ganglionic neurons after infection allocates the BHV-1 virus to persist in the body and spread the disease from a latently infected carrier to a non-infected herd. The first report of BHV-1 infection was recorded as genital form of disease as infectious pustular vulvo-vaginitis (IPV) in cattle in 1841 in Germany. Viral association with this form of disease was confirmed in 1928; respiratory form (IBR) was observed in 1950s and in 1958 for the first time the virus was isolated successfully and classified in the family Herpesviridae. BHV-1 is currently widespread all over the world, and observed in USA, Canada, Zaire, Italy, Belgium, India, Japan, Taiwan and Turkey. The documented prevalence of BHV-1 is 83% in UK, 63%–86% in Eygpt, 43% in England, 36%–48% in Central and South America, 36% in China, 14%–60% in Africa and as restricted distribution in India. Among East and South Asian countries in Nepal, Sri Lanka, Korea, Bhutan and Bangladesh disease was not reported. BHV-1 virus has been detected in many states of India, like Uttar Pradesh, Uttarakhand, Haryana, Kerala, Punjab, Chhattisgarh, Gujarat, Maharashtra, Tamil Nadu, Orissa, Arunachal Pradesh, Nagaland and Karnataka with maximum prevalence in Uttar Pradesh and minimum in Himachal Pradesh. Considering the emerging nature of virus, latency, unusual rate of spread of the infection with economic aspects, the current scenario of BHV-1 in South and East Asian region is addressed to formulate a comprehensive control strategy involving thorough screening before international trading and restricting animal movements between different parts of world.

Naresh Jindal

Lala Lajpat Rai University of Veterinary and Animal Sciences,India

Title: Enteric viruses in chicken enteritis

Time : 11:50 - 12:10

Speaker
Biography:

Dr. Naresh Jindal completed his PhD from Chaudhary Charan Singh Haryana Agricultural University, Hisar (India) in 1999. He pursued his Post-Doctoral studies for a period of two years (2007-2009) at the University of Minnesota, College of Veterinary Medicine, St Paul, USA. He is at present a Senior Disease Investigation Officer, Department of Veterinary Public Health and Epidemiology, College of Veterinary Sciences, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar (India). His thrust area of working is diagnosis and epidemiology of viral diseases poultry. He has published more than 50 papers in reputed journals.

Abstract:

Health of gastro-intestinal tract is important to get maximum returns in terms of body weight gain and egg production in chicken. Enteric diseases such as runting and stunting syndrome, malabsorption syndrome hamper the production potential to be achieved to its maximum. A number of viruses, bacteria and protozoa have been detected and characterized from enteric cases but the primary etiology has not been definitively established. Previously, electron microscopy was used to detect the presence of enteric viruses. Due to similarities in the viral morphology, there are chances of misidentification by electron microscopy. With the advent of molecular diagnostic methods and next generation sequencing, researchers have made long strides in identification and characterization of viruses associated with enteritis. The molecular techniques have also helped us in identification of enteric pathogens which were previously not known. Regional and national surveys have revealed the presence of several different viruses in enteritis cases including rotavirus, astrovirus, avian nephritis virus, orthoreovirus, picobirnavirus, adenovirus, and coronavirus. These viruses have been detected either alone or in combination. Detection of more than one virus in enteric cases indicates that multiple viruses may be involved in the pathogenesis of enteritis. There may still be unknown pathogens that may directly or indirectly play a role in enteritis in chickens. Detection of unknown viruses by the metagenomics approach would pave the way to develop diagnostic methods for these viruses. At present, there is no specific treatment, and commercially available vaccines have not yet been developed for the viruses that are involved in enteritis in chickens. Complete understanding of the contribution of enteric viruses and other pathogens in enteric diseases of chickens will help in the development of preventive and control measures.

Souvik Ghosh

University School of Veterinary Medicine,West Indies

Title: Whole Genomic Analysis of Rotaviruses

Time : 12:10 - 12:30

Speaker
Biography:

Dr. Souvik Ghosh is an Assistant Professor and DVM course director of Virology at the Ross University School of Veterinary Medicine, West Indies. He holds degrees of Bachelor of Veterinary Science, Masters in Veterinary Medicine & Public Health, and Ph.D. (Virology). Dr. Ghosh is a well-known expert on rotaviruses, a major cause of diarrhea worldwide. He has published more than 60 research papers and reviews in peer reviewed international journals. Dr. Ghosh serves as the section editor of Archives of Medical Science and Austin Journal of Virology and Retrovirology, and acts as reviewer to more than 15 international virology/microbiology journals.

Abstract:

Rotavirus-A (RVA) are a major cause of viral diarrhea in humans, animals and birds. The RVA genome consists of 11 segments of double-stranded RNA that encode 6 structural and 6 nonstructural proteins. The mechanisms of genetic diversity of RVAs include reassortment, point mutations and rearrangement events. Whole genomic analyses of RVA strains from different host species are essential to obtain conclusive data on the complex evolutionary patterns, interspecies transmission/zoonosis, and reassortment events of rotaviruses. In 2008, the whole genome-based RVA genotyping scheme was introduced, providing researchers with a uniform platform to study the overall genetic diversity of RVAs. Since then, we have performed whole genome sequencing on several RVAs detected in humans, cattle, pigs and horses, including archival and reference strains. Analyses of these RVA whole genome sequences provided a plethora of conclusive, crucial, and/or new data on (i) emergence of novel RVA genotypes, (ii) zoonosis including the first conclusive evidence for transmission of RVAs from wildlife (simian) to humans, (iii) interspecies transmission of RVAs between farm animals, (iv) reassortment events involving RVAs from different host species including those between human and animal RVA strains, and (v) rare inter-genogroup reassortment events. Taken together, our findings provided vital insights into the complex genodynamics and interspecies transmission of RVAs, with implications on public health.

Speaker
Biography:

Xiufan Liu, completed his DVM at the age of 25 from Yangzhou University. He is currently a professor of Yangzhou University. His research areas focus on the epidemiology and pathogenesis of major infectious diseases in poultry in the last two decades with more than 100 papers in reputed journals.

Abstract:

Newcastle disease (ND) is caused by virulent Newcastle disease virus (NDV), which leads to heavy economic losses to poultry industry. Even though intensive vaccination programs have been implemented in many countries, virulent NDV can still be frequently isolated in well-vaccinated flocks. We tested the protection efficiency of LaSota and two sub-genotype VIId vaccines, NDV/AI4 and O/AI4, while O/AI4 was constructed by replacing the HN gene of the vaccine strain NDV/AI4 with that of the variant NDV strain JS-14-12-Ch. The cross-neutralization and Cross-hemagglutination inhibition tests between JS-14-12-Ch and the three vaccine strains indicated the significant antigenic difference between JS-14-12-Ch and LaSota as well as NDV/AI4, but not between JS-14-12-Ch and O/AI4. The results of vaccine protection tests showed that O/AI4 provided improved protection as determined by a significant decrease in both the number of birds shedding, the amount of virus shedding, and virus replication in visceral organs from challenged birds. This study suggested that ND vaccine strain which antigenically and genetically matches with prevalent field strains provides significant better protection than the conventional ones, in terms of reducing virus shedding and transmission.

Speaker
Biography:

Graduated in Biological Sciences from the Pontifícia Universidade Católica de Minas Gerais, Brazil (1985); Masters in Biochemistry and Immunology - Department of Biochemistry and Immunology / UFMG (1990), Belo Horizonte, Brazil; Sandwich Doctorate in Biological Sciences (Biochemistry) from the Federal University of Rio Grande do Sul, Rio Grande do Sul,Brazil (1998) and "Plum Island Animal Disease Center," USDA, USA; Post-doctorate in Molecular Biology of Viruses in "Plum Island Animal Disease Center," USDA, USA. She is currently Head of the Department of Biochemistry and Molecular Biology, Professor, Coordinator of the Laboratory of Animal Molecular Infectology / BIOAGRO at the Federal University of Viçosa, Viçosa, Minas Gerais, Brazil. She has published more than 40 papers in reputed journals. She has experience in Agricultural Biochemistry and Preventive Veterinary,with an emphasis on molecular biology of animal viruses, acting on the following subjects:Molecular Infectology, Diagnosis, Recombinant vaccines and Antivirals.

Abstract:

In Brazil, our research group has focused on epidemiology and control of Porcine circovirus-2(PCV-2). Porcine circovirus-2 is an emerging virusassociated with a number of different syndromes in pigs known as Porcine Circovirus Associated Diseases (PCVAD). Since its identification and characterization in the early 1990s, PCV-2 has achieved a worldwide distribution, becoming endemic in most pig-producing countries, and is currently considered as the main cause of losses on pig farms. Our research group has analyzed the main routes of the spread of PCV-2 between pig-producing countries using phylogenetic and phylogeographical approaches. Our approaches consists on analyze all information about PCV-2 sequences available in GenBank, including papers published on viral isolation, and live pig trading statistics available on the UN Comtrade database (http://comtrade.un.org/). We have found a strong correlation between the means of PCV-2 dispersal predicted by phylogenetic analyzes and the statistics on the international trading of live pigs. Recently, we present the first description of PCV2d genotype in Brazil associated to a PCVAD outbreak. Our researches has contributed to a better understand the origins of PCV-2 in Brazil and its dispersal around the world.

Eduardo N. Esteban

National University of Central Buenos Aires (FCV-UNCPBA),Brasil

Title: Bovine Leukaemia Virus (BLV) true resistant cattle truncate virus transmission
Speaker
Biography:

Eduardo N. Esteban is working as Professor of Biology at Faculty of Veterinary Sciences UNCPBA.In the year 1981-1983 he was Post Doctoral Fellow in Bovine Leukemia Research Center. The School of Veterinary Medicine University of Pennsylvania. U.S.A.

Abstract:

Economic losses in Argentina and particularly in subtropical regions are high due to BLV-induced leukaemia/lymphoma mortality plus reduction of milk production by BLV-infected cows. BLV-prevalence in the Departamento Rivadavia (Santiago del Estero Province) by 2011-2012 was 84.1% in dairy cattle. Facing such a high prevalence, controlling the virus by serological detection of BLV-infected cattle and culling from the herd is no longer an economically feasible option. No vaccine or therapeutic procedures to avoid BLV dissemination is available so far and controlled breeding of BLV-naturally resistant cattle selected by marker assistance rises as a unique tool to fight BLV. The effectiveness of this procedure depends on the premise that BLV-resistant cattle should not be an infection source for BLV-negative animals. Some BLV-infected animals develop the infection phenotype known as Low Proviral Load (LPL). The BLV-infection phenotypes are associated with the polymorphism of the bovine MHC Class II BoLA-DRB 3.2*. Allele BoLA-DRB3*0902 has the strongest association with LPL-phenotype. More than 80% of cattle selected by BoLA DRB3*0902 genotyping develop LPL when infected with BLV. To test under natural conditions whether these cattle break the BLV-transmission chain, selected BLV-infected LPL-BoLA-DRB3*0902 heterozygous cows were incorporated into a BLV-negative dairy herd. An average ratio of 5.4 (range 4.17-6.37) BLV-negative cows per BLV-infected cattle was kept during 20 months of experiment. Under the same conditions, non-characterized BLV-infected cows were mixed with BLV-negative animals to estimate the BLV-incidence rate (Irate) which was 0.0654%. Predicted BLV-prevalence for the entire region through 9 years using the estimated Irate was just slightly higher than observed BLV-prevalence. Instead, while the Irate predicted 20 new BLV-positive cattle after 20 months in contact with selected BLV-infected LPL-BoLA-DRB3*0902 animals, no BLV-negative cattle became infected. Conclusion. These results confirm for the first time that LPL-BoLA-DRB3*0902 cattle are indeed BLV-resistant and a feasible approach to control the virus.

Rajesh Kumar Joshi

College of Veterinary Science and Animal Husbandry,India

Title: Canine Parvo virus: A cause of concern in canines
Biography:

Prof Rajesh Kumar Joshi has completed his Ph.D. in Veterinary Microbiology and Public Health in year 1994 from G.B. Pant University of Agriculture and Technology, Pantnagar, India. Presently, He is Head of Department of Veterinary Microbiology at College of Veterinary Science and Animal Husbandry, N.D. University of Agriculture and Technology, Kumarganj, Faizabad (India). He has the teaching experience of over 20 years in Veterinary Microbiology and published more than 70 papers in reputed journals and has been serving as an editorial board member of reputed Journals

Abstract:

Canine parvovirus (CPV) represents a well-documented example highlighting the emergence of a new virus through cross-species transmission. CPV emerged in the mid-1970s as a new pathogen of dogs and has since become endemic in the global dog population. Despite widespread vaccination, CPV has remained a widespread disease of dogs and new genetic and antigenic variants have arisen and sometimes reached high frequency in certain geographic regions or throughout the world. Members of the parvovirus genus infect a wide variety of mammalian hosts and are characterized by more or less strict host specificity. Carnivore parvovirus only infects actively dividing host cells. The clinical manifestations of disease are strongly dependent on the age of the host and the symptoms are similar in wild as well as domestic animals. Most cases of CPV infections are caused by a genetic alteration of the original canine parvovirus CPV- 2b. There are a variety of risk factors that can increase a dog’s susceptibility to the disease, but mainly, the virus is transmitted either by direct contact with an infected dog, or indirectly, by the fecal-oral route. Heavy concentrations of the parvovirus are found in the feces of an infected dog. In spite of a large number of vaccine strains and vaccination regimens are in use, there is a sharp rise in the cases of parvovirus infection in vaccinated dogs. Such infections are mostly reported to have severe symptoms and high mortality. These reports suggest the requirement for a thorough study of the clinical field isolates to find out the reasons of such changes at virus level.

Speaker
Biography:

Md.Bahanur Rahman is working as professor in Department of Microbiology and Hygiene in Bangladesh Agricultural University,Bangladesh.

Abstract:

Present study was undertaken to find out seroprevalence of avian influenza virus with molecular detection of this virus circulating in chicken and duck of selected areas in Bangladesh. For these purpose, a total of 360 swab samples (cloacal and oropharyngeal) and 360 serum samples were collected from Rajshahi, Netrokona, Sherpur, Kishoregonj. All samples were subjected to slide HA test and 60 (16.67%) samples found positive. Out of 60 HA positive samples, 45 samples were from Chicken (broiler 15%, layer 31.67%, backyard chicken 28.33%) and 15 (8.33%) from duck. By using AIV Ag detection Rapid Test Kit (RTK) test, all 360 collected swab samples were tested and 43 (11.95%) samples from chicken and duck were fund AIV positive. Among these RTK positive samples, 31samples were (broiler 8.33%, layer 23.33%, backyard chicken 20.0%) from chicken and 12 (6.67%) from Duck. Genus specific M gene possessed in 24 (6.67%) samples, among these 14 (3.89%) isolates possessed HA and NA gene (H5N1) using H5 and N1 specific primer. The HPAIV (H5N1) isolated from 11 chicken samples (broiler 1.67%, layer 10%, backyard chicken 6.67%) and 3 (1.67%) duck samples. Of 360 sera samples, 116 (32.22%) were found positive for avian influenza virus Ab in ELISA. Among them, 16 from chicken (broiler 5%, layer 13.33%, backyard chicken 8.33%) and 100 (55.55%) from duck. Data from this study revealed that, Netrokona district was found more vulnerable to HPAI, (RTK positive 24.44%, HA positive 32.22%, RT-PCR assay M gene positive 17.77%, H5N1 positive 10% and 48.88% sera were Ab positive in ELISA). From this study it is also revealed that HPAI virus spreads rapidly in winter season in comparison to other period of the year. From this study it could be concluded that ducks may act as a carrier of pathogenic AIV in Bangladesh.

  • Special Lecture

Session Introduction

Dharam Ablashi

KHG fiteBac Technology,HHV-6 Foundation,USA

Title: The Antimicrobial Compound, K21, Inhibits Replication of Enveloped and Non-Enveloped DNA and RNA Viruses

Time : 13:10 - 13:40

Speaker
Biography:

Dharam V. Ablashi is a microbiologist. He has published over 300 articles on herpesviruses and HIV. His major interests are assessing pathogenic roles of viruses in diseases, and in developing antivirals as therapeutic reagents. He has a BSc, and a D.M.V from Panjab University India, a Dip. Bact from I.V.R.I, and MS in Virology from the University of R.I., USA. He worked 23 years at NIH. In 1986, he co-discovered human herpesvirus-6 (HHV-6), a highly neurotropic and immune suppressive virus. He was as an adjunct professor at Georgetown University School of Medicine, Washington, DC, and Director of Herpesvirus Research in a diagnostic company. Currently, the Scientific Director of the HHV-6 Foundation, and the Senior Technology Adviser at KHG fiteBac Technology in Marietta, Georgia.

Abstract:

The K-21 derivative of Quaternary Ammonium Compound (QAC: Dow Corning C5700), as formulated by Dr. Kimmerling in 2011, shows antimicrobial and antifungal activity with minor toxicity. We tested K-21 at different concentrations in different solvents on HSV-1 and HHV-6, and Influenza A, Strain H1N1. HSV-1 replication, and similarly HHV-6 were significantly inhibited as measured by cytopathic effects (CPE), PCR, and inhibition of viral proteins by western blots with a concentration of 0.025%. Influenza A and two non-enveloped RNA viruses (Phage MS2, a surrogate of polio virus and feline norovirus) were also inhibited by K-21 solution within 10 minutes contact. Influenza A was significantly inhibited by lower concentrations of K-21. The two nonenveloped viruses, however, were inhibited by <55%. Higher concentrations of K-21 (0.1%) were required to significantly inhibited feline virus (>98%). While concentrations of 0.025% K- 21 were not toxic, the 0.1% K-21 concentration showed some toxicity yet was tested at only one dilution. K-21 anti-viral effects on HIV-1 strains is currently explored. K-21 is a unique antiviral, antibacterial, and antifungal agent, which is potent germicidal topical application against various infections. Further studies are in progress for in vivo applications as a spray or as a hand gel and in other forms for human use.

  • Symposium

Session Introduction

Maged Gomaa Hemida

King Faisal University, Saudi Arabia

Title: The Current Emerging and Re-emergent Viral Diseases Threats

Time : 13:40 - 14:10

Speaker
Biography:

Dr. Hemida received his Ph.D from University of Guelph, 2009. He pursued his PDF training at the the University of British Columbia (James Hogg iCapture Centre). His research area of interest is “One Health Concept” with special emphasis on emerging viruses/host interaction. Currently, studying the molecular evolution and pathogenesis of MERSCoV in the Middle East. He published more than 40 original Research papers on high impacted journals. Meanwhile, he received several Research grants, prestigious honors and scholarship throughout his academic carrier. Currently, he is a reviewer of many granting agencies as well as editorial board member of many international journals

Abstract:

  • Viral Immunology
Speaker

Chair

C. Yong Kang

Western University,Canada

Speaker

Co-Chair

Maged Gomaa Hemida

King Faisal University, Saudi Arabia

Session Introduction

Bala Chandran

Rosalind Franklin University of Medicine and Science,USA

Title: Nuclear innate sensor IFI16 recognition of hepresviral genomes and inflammasome and IFN-β responses

Time : 14:10 - 14:30

Speaker
Biography:

Dr. Chandran received his M.S. from JIPMER, Pondicherry, and his Ph.D. degree from AIIMS, New Delhi, India in 1979. Dr. Chandran's postdoctoral experience includes positions at the Cancer Research Group at McMaster University, Hamilton, Ontario, Canada and at the University of Florida, Gainesville. He was appointed Assistant Professor in the Department of Microbiology, University of Kansas Medical Center in 1986, and then Professor in 1996. Dr. Chandran joined the Department of Microbiology and Immunology at Rosalind Franklin University of Medicine and Science on July 1, 2005 as Professor and Chair. He has published more than 150 papers

Abstract:

The innate immune system NOD-like and AIM2-like receptors are cytoplasmic inflammasome sensors of foreign molecules, including DNA and elicit pro-inflammatory IL-1, IL-18 or interferon β (IFN-β) responses. We have shown that IFI16, a sequence-independent nuclear innate sensor, recognizes the episomal dsDNA genomes of herpes viruses such as KSHV, EBV, and HSV-1 in the infected cell nuclei, forms an inflammasome complex with ASC and procaspase1, and relocates into the cytoplasm leading into Caspase-1 and IL-1β generation. IFI16 also induces IFN-β during HSV-1 infection via the cytoplasmic STING-IRF3 pathway. Whether IFI16 recognizes foreign DNA directly or utilizes other host protein(s), and the mechanisms of IFI16-inflammasome formation, cytoplasmic redistribution and STING activation were not known. Our studies demonstrate that BRCA1 is in complex with IFI16 in the host cell nucleus, and their association increases in the presence of nuclear viral genomes during de novo KSHV, EBV and HSV-1 infection, and in latent KSHV or EBV infection. Our findings highlight that BRCA1 plays a hitherto unidentified innate immunomodulatory role by facilitating nuclear foreign DNA sensing by IFI16, assembly and cytoplasmic distribution of IFI16-inflammasomes, IL-1β and IFN-β formation. Our studies also demonstrate that recognition of herpesvirus genomes in the nucleus by IFI16 leads into its interaction with histone acetyltransferase p300 and IFI16 acetylation resulting in IFI16-ASC interaction, inflammasome assembly, cytoplasmic redistribution, caspase-1 activation, IL-1β production, interaction with STING, and IFN-β production. Collectively, our studies identify the increased nuclear acetylation of IFI16 as a dynamic essential post-genome recognition event in the nucleus that is common to the IFI16-mediated innate responses of inflammasome induction and IFN-β production during herpesvirus infections.

Speaker
Biography:

C. Yong Kang has completed his PhD from McMaster University in Canada and post-doctoral training at the University of Wisconsin-Madison. He served as a Professor of Virology at the University of Texas Southwestern Medical School, Professor and Chairman at the University of Ottawa Faculty of Medicine, and Dean of Science at the University of Western Ontario. He has published 137 peer reviewed research papers and 151 scientific proceedings and abstracts. He holds nine international biotechnology patents. He received numerous awards including the Ho-Am Prize in Medicine. He is a Life-time Fellow of the Royal Society of Canada Academy of Science. He serves as a reviewer for eight international journals.

Abstract:

In order to induce the maximum immune responses, the priming recombinant viral vector should be antigenically distinct from the boost vaccine vector. We have engineered safer and highly efficient recombinant vesicular stomatitis virus (VSV) vaccine vectors using two antigenically distinct Indiana serotype (VSVInd) and New Jersey serotype (VSVNJ). The M51R mutation in the M gene of VSVInd was combined with a temperature sensitive mutation of the VSVInd Orsay tsO23 for priming vaccine vector [rVSVInd(GML)]. In addition, we have engineered VSVNJ vaccine vector by combining M48R+M51R mutation with G22E and L110F mutations in the M gene of VSVNJ [VSVNJ(GMML)] for boosting vaccine vector. The combined mutations of G21E/M51R/L111A in the M protein of VSVInd [rVSVInd(GML)] significantly reduced the burst size of the virus by up to 10,000 fold at a semi-permissive temperature of 37°C without affecting the level of protein expression. Mice injected with one million infectious particles of rVSVInd(GML) into the brain showed no neurological dysfunctions or any other adverse effects. In contrast, only one thousand wild-type VSVInd killed mice within four days. To examine the CD8+ T cell and B cell responses against the proteins of interest expressed from the rVSV vectors, we generated rVSVs with HIV-1gag, pol and/or env genes. From the various vaccination regimens tested in mice, priming with rVSVInd(GML)-HIV-1gag, pol, and/or env and boosting with rVSVNJ(GMML)-HIV-1gag, pol, and/or env induced the strongest CD8+ T cell immune responses against HIV-1 Gag, Pol, and Env proteins. The same vaccination regimen also induced strong humoral immune responses against HIV-1 Gag and Env proteins in mice. This is our unique platform technology and is useful for development of vaccines against many other viral diseases.

Speaker
Biography:

Dr. Hye Kyung Chung completed her Ph.D from Kun-kuk University, and subsequently studied the pathogenesis and molecular mechanism of retroviruses as a postdoctoral fellow at the National Institutes of Health. She is a senior staff scientist at ABL, a contract research and manufacturing service organization. The majority of her research career has been studying anti-viral immunity, molecular virology, and pathogenesis of human and animal lentiviruses. She currently studies NHP models of retroviral latency and reactivation. Dr. Chung continues to develop cutting-edge new assays to study vaccines, pathogenesis, and viral reservoirs.

Abstract:

We previously identified distinct gene expression profiles in peripheral blood mononuclear cells of viral controllers versus non-controllers. To further define the molecular mechanisms of protective innate and adaptive immune responses elicited by heterologous challenge, we re-challenged SHIV-infected macaques that had undetectable levels of viremia with SIV mac251, and compared the gene expression profiles of different infection outcomes. MHC-1 protective alleles contributed in part to limit viral replication, although the control of virus by adaptive immunity could not be ruled out. Plasma viral RNA load was markedly controlled in four of the challenged animals at the set point (protectors), conversely two animals had persistent high viremia throughout the monitoring period of 160 days (non-protectors). Analysis of the cellular gene expression profiles in the CD4+ T cells at early time points from all tested animals revealed distinct gene expression signatures between protectors and non-protectors. Using the Local-Pooled-Error test specifically designed for analyzing gene expression data with a small sample size, eight genes (MX1, MX2, IFI27, JAK2, LMO2, TYROBP, ‘FCN1, and S100A9) were identified as potential protective biomarkers, after adjusting for the large number of false positives from the high throughput gene expression data analysis. Pathway analyses revealed that these 8 genes are associated with the IFN pathway, and are down-regulated in protectors compared to non-protectors. This study suggests that high level expression of type 1 IFN-related genes may paradoxically promote virus replication.

Pavel Bostik

Charles University School of Medicine ,Czech Republic

Title: Mechanisms of apoptosis induced in immune cells directly od indirectly by virus infection

Time : 15:10 - 15:30

Speaker
Biography:

Pavel Bostik completed his MD at Charles University School of Medicine in Prague, Czech Republic in 1990 and his PhD at FMHS in Czech Republic. He conducted his postdoctoral studies the University of Iowa School of Medicine. He subsequently worked at the Emory University School of medicine in Atlanta, GA until 2009. He is the Vice Dean for Research at the FMHS and Professor at Charles University School of Medicine in Hradec Kralove, Czech Republic. He has published more than 50 papers in reputed journals. His focus is in the effect of viral infections on intracellular signaling in T cells

Abstract:

Apoptosis of immune cells is an important factor in pathogenesis of certain viral diseases. Specifically those viruses, which target directly immune cells - e.g. lymphocytes - manifest often, at least in part, with increased cell death with consequent immune deficits. Typically in the diseases like HIV infection, the virus targets CD4+ T cells, which then undergo apoptosis or activation induced cell death at an increasing rate. Other viruses, e.g. some herpetic viruses are known to infect immune cells, but the role of this infection in the immune response of the host is not clear. The potential of other viruses, such as HCV, to target directly immune cells is still being discussed. Several pathways, which can serve as targets for virus-induced dysregulation of immune cells, can have a significant effect on apoptosis. One of the important ones is mediated by Akt kinase. This kinase is regulated mainly by phosphorylation of two sites - Ser473 and Thr310. The phosphorylation status of these sites dictates downstream signaling through GSK3beta, which manifests by phosphorylation of its Ser9 site. We show, that several viruses mentioned above exert significant effects on this pathway, which, in turn, correlates with the rate of apoptosis of T lymphocytes.

Speaker
Biography:

Vladimir Berezin has completed his PhD at the age of 28 years from Ivanovsky Institute of Virology in Moscow (Russia) and postdoctoral studies in same Institute. He was a director of the Institute of Microbiology and Virology in Almaty, Kazakhstan. Currently he is the head of Department of Virology in the Institute of Microbiology and Virology in Almaty, Kazakhstan

Abstract:

Highly purified low toxicity immunostimulatory triterpen saponins GlabiloxTM and AsgipanTM were isolated from Glycyrrhiza glabra and Aesculus hippocastanum plants indigenous to Kazakhstan. These saponins were used for assembling of immunostimulating nanocomplexes (ISCOMs) contained purified HA and NA influenza virus antigens and for preparation of saponin/lipid particulate SAPOMAX adjuvant. Immunostimulation activity and protection capacity of two kinds of influenza vaccine preparations: subunit vaccine based ISCOMs and whole virus inactivated influenza vaccine contained SAPOMAX adjuvant were studied in mice immunization experiments at intranasal and subcutaneous routes of immunization. It was shown that single intranasal immunization of subunit vaccine based ISCOMs contained GlabiloxTM or AsgipanTM saponins stimulated high levels of IgM, IgA, IgG1, IgG2a and IgG2b antibody, good production of IL-2, IL-4, IL-10 and IFN-γ cytokines and protected animals against lethal influenza virus infection. Activity of antibody and cytokines production as well as protective immunity after single intranasal immunization of ISCOMs vaccine was comparable with immune responses and protection after subcutaneous administration of vaccine preparation. Whole virus inactivated influenza vaccine mixed with SAPOMAX adjuvant was studied in mice immunization experiments at intranasal route of immunization. It was shown that intranasal immunization of whole virus inactivated influenza vaccine mixed with SAPOMAX adjuvant stimulated high levels of antibody and cellular immune responses and protection against lethal influenza infection. The results of study have shown that purified triterpen saponins GlabiloxTM and AsgipanTM isolated from plants indigenous to Kazakhstan may be used as efficient adjuvants for creation of influenza vaccine preparations intended for mucosal (intranasal) immunization.

Speaker
Biography:

Dr. Azra Fatima completed her PhD in 2011 at the University of Cologne, Germany. She continued Postdoc fellow for one year and subsequently she became an independent group leader of the Cologne-Fortune research grant in 2014. Dr. Fatima worked in active collaboration with the University of Harvard and University of North Carolina. Dr. Fatima research efforts led to have excellent publication track record in the fields of human and murine embryonic stem cell and cardiovascular disease modeling by generating human cardiovascular diseased patient fibroblasts reprogrammed into human induced pluripotent stem cell (hiPS) for cardiomyocytes generation for the heart transplantation potential. She used retroviral vectors integrated with reprogramming factors in it to generate hiPS.

Abstract:

Human somatic cells can be reprogrammed into induced pluripotent stem cells (iPS). iPS cells have a regenerative potential similar to that of human embryonic stem cells (ES cells), which may serve as source of cells for tissue repair (transplantation), in-vitro disease modelling and drug toxicity assays. A number of methods have been developed for converting adult somatic cells into a pluripotent from which ethically acceptable patient specific mature cells of interest can be derived. Successful reprogramming of skin fibroblasts to iPS cells can be achieved by ectopic expression of stemness factors. Here, I will discuss the various conventional methods of reprogramming using lenti-virus, retro-virus, adeno-virus and sendai-virus as a viral vectors. These methods although had a lot of disadvantages but led to fast progress in the stem cell research fields. The pros and cons of the use of viruses for reprogramming will be discussed with the advancement in the field a lot of non-viral approaches, which has been recently introduced.

  • Organ specific Cancer and Tumor virology

Session Introduction

Miguel Angel Mendoza Catalan

Autonomous University of Guerrero,Mexico

Title: E6 of HPV-16-variants induces invasive capacity of C-33A: Ezrin as regulator of this process

Time : 16:10 - 16:30

Speaker
Biography:

Dr. Miguel Angel Mendoza Catalan has completed his PhD in Biomedical Sciences at age of 29 years from University of Guerrero State, Mexico. He is a young researcher member of National System of Researchers, Mexico. Actually he is Researcher Professor in the University of Guerrero, expert in cell biology, assigned to the laboratory of Molecular Biomedicine at the school of Chemical and Biological Sciences. He has published one paper in reputed journals and two more in process about expression of proteins and mechanisms of cell motility and invasion of cervical and breast cancer cells.

Abstract:

The cervical cancer is the second cause of death from malignancy in women of reproductive age. The Human Papillomavirus high risk (HR-HPV) is the necessary biological factor for development of malignant lesions in the cervix, in collaboration with other factors. It has been reported that HPV-16 is the most frequent in the cases of cervical cancer, and that oncogenic risk may vary according to the genetic variants of virus. In women in southern Mexico, it has been observed that the most frequent variants in cases of cervical cancer are AAa, AAc, E-G350, E-C188/G350 and E-C176/G350. Some studies show that HPV 16 oncoproteins, E6 particularly, promote invasiveness of cervical tumor cells by overexpression of several matrix metalloproteinases, which are proteases responsible for degradation of extracellular matrix, which initiates and promotes the cell invasion process. In our laboratory, C33A cells expressing the E6 oncoprotein of HPV16 variants more frequent in Guerrero state were generated. Using RNA microarrays, we observed that expression of E6 in these cells affects the expression of several genes that, among other processes, are involved in adhesion, cell motility and signalling having a different effect for each variant of HPV16. We are evaluating the invasive capacity of cells expressing E6 for each HPV-16 variant and the mechanisms involved; participation of Ezrin, an invasivity regulator in other cancers, and the expression and activity of MMPs, as well as the Vimentin and E-cadherin expression, proteins involved in epithelial mesenchymal transition, which promotes the cell motility of tumor cells. Preliminary, we have observed that E6 HVP-16-AA induces major invasive capacity in comparison with the other variants and cells control, and this effect is Ezrin dependent. This research helps understanding of the mechanisms of invasion of cervical tumor cells induced by HPV E6 and the regulators of this process.

Speaker
Biography:

Dr. Silva has completed her PhD at Princeton University and postdoctoral studies from Mount Sinai School of Medicine and University of Texas Medical Branch. She is professor at UFABC, in São Paulo and works with the relationship between HCMV and cancer.

Abstract:

Gliomas are the most common brain tumors in adults and are divided into ependymomas, astrocytomas, oligodendrogliomas, and mixed oligo-astrocytomas. Based on malignant tumor behavior, astrocytomas are divided in grade I, II, III and IV and oligodendrogliomas in grade II and III. The higher the grade, the worse the prognosis. One of the most controversial areas regarding brain tumors is the relationship between human cytomegalovirus (HCMV) and gliomas. Multiple studies showed the presence of viral nucleic acids and proteins in these tumors, and it has been demonstrated that several viral proteins have the potential to increase cell malignancy. Although the majority of the studies showed a positive association, there are still reports that fail to detect the HCMV in gliomas, and the presence of the virus is a topic of debate and an issue that needs to be resolved. We investigated the presence of HCMV DNA by qPCR in gliomas with different grades of malignancy from Brazilian patients. The UL83 viral region was detected in 4/7 (57%) Astrocytomas I, 9/11 (82%) Astrocytomas II, 7/8 (88%) Astrocytomas III, 6/10 (60%) Astrocytomas IV, 5/7 (71%) Oligodendrogliomas II and 4/7 (57%) Oligodendrogliomas III. In astrocytomas the HCMV DNA copy number correlates with tumor progression until grade III. However it decreases at level IV, possibly due the high levels of necrotic areas in the tissue. Our results confirm the presence of HCMV in gliomas and indicate that there is a correlation of virus presence and tumor progression, supporting further investigation of the virus’ oncomodulatory properties.

Masaaki Kawano

Saitama Medical University.Japan

Title: Medical application of a nanocapsule derived from a viral capsid protein

Time : 16:30 - 16:50

Speaker
Biography:

Masaaki Kawano has been engaged in the study of the in vitro assembly of simian virus 40 (SV40) virus-like particles (VLPs) composed of VP1 capsid for 10 years, from the beginning of his career. He has currently focused on the development of a novel vaccine carrier consisting of SV40 VP1 for cytotoxic T lymphocyte (CTL)-based vaccines against latent infection and cancer

Abstract:

Development of protein-based delivery-carriers for diagnosis and therapy has progressed by using viral capsid protein. Simian virus 40 (SV40) is a small non-enveloped DNA virus of polyomaviridae. The capsid structure of SV40 is 45 nm in diameter and is formed by 72 copies of pentamers composed of five VP1 major capsid proteins (360 molecules in total). When expressed in insect cells using recombinant baculovirus, VP1 is self-assembled into virus-like particles (VLPs) of 45 nm in diameter as the naturally assembled SV40 virus capsid. VLPs isolated from the cells are disassembled in vitro into VP1-pentamers by the addition of DTT and EGTA. These VP1-pentamers are self-reassembled in vitro into VLPs under appropriate conditions. In this reassembly, VLPs can encapsulate various materials such as DNA and proteins. It is also possible to modify VP1 for providing VLPs with the ability of targeting of specific cell. It was recently indicated that SV40 VLPs could be a promising vaccine platform. Thus, VP1 has a great potential for developing a variety of nanocapsule for medical application. In this presentation, we summarize our technology using SV40 VP1 for medical application and show an application of SV40 VP1 as an efficient vaccine nanocapsule. Indeed, vaccination of SV40 VP1 nanocapsule inserted HLA-A2 restricted cytotoxic T lymphocyte (CTL) epitope of GILGFVFTL of influenza virus matrix protein 1 (M1) efficiently induced CTLs against M1 with fifty times more than classical incomplete freund’s adjuvant method.

Biography:

Grace Pennap is a Microbiology Lecturer with Nasarawa State University Keffi. Her field of interest is Viral Epidemiology where she has 39 peer reviewed publications in reputed Scientific Journals and has contributed a chapter each in two text books.

Abstract:

Nigeria has the largest burden of children living with HIV in the world but because of antiretroviral therapy, they are living longer. However, hepatitis B and C viruses are emerging important co-morbidities to consider especially for management decisions. This study set out to determine the prevalence of hepatitis B and C viruses among these children and to identify possible risk factors associated with the infections. Two hundred HIV-infected children at an antiretroviral treatment center were screened for Hepatitis B and C seromarkers using rapid test kits (ABCON Laboratories Hangzhou China). Informed written consent was obtained from their parents/guardians. Information on their sociodemographics and exposure to some possible risk factors were obtained. A general prevalence of infection with hepatitis B and C virus in the study population was 14.0%. The prevalence of HBV was 3.0% while HCV was 11.0% and no child was coinfected with all 3 viruses. There was no statistically significant association between coinfection with either of the hepatitis viruses and the studied parameters (p>0.05). This does not down play the importance of the coinfection. The HIV/HBV and HIV/HCV coinfection prevalence of 3.0% and 11.0% respectively is a cause for alarm. It is therefore pertinent that HIV infected children are screened for these viruses before commencement of Antiretroviral therapy.

Speaker
Biography:

Dr Zil-e-Rubab is a medical doctor graduated from from King Edward Medical University. She has special interest in virology research. Currently she is associated with Ziauddin University, Karachi as Professor of Biochemistry. Currently, she is working on project related to human papilloma virus in oral cavity.

Abstract:

In Pakistan oropharyngeal cancer is the second leading malignancy attributed to the extensive use of smokeless tobacco products. In many studies, the high risk genotypes of HPV are proven to play a key role in oral squamous cell carcinoma (OSCC).There is a considerable diversity in the epidemiology of high risk HPV genotypes in different countries. The objective of this study was to find out the association between high risk HPV genotype in oral rinse of patients with OSCC and pre malignant oral lesions. In this case-control study, 200 samples of oral rinse were analyzed by PCR. A significant association between HPV and OSCC was found (OR=3.14, 95% CI=1.6750-5.8969, P value=0.0004).There was positive association between presence of both HPV 16/18 and OSCC but it was not significant possibly due to small sample size (OR=3.2381, 95% CI=0.8208-12.7752, P value=0.0934). As a result of these findings, HPV and predominantly genotypes 16 and 18 may be associated with the development of OSCC in Pakistan.

Speaker
Biography:

Sita Awasthi has received her Ph.D in Biochemistry from Devi Ahilya University at Indore, India and her postdoctoral training from University of Pennsylvania at Philadelphia. Currently she is a Research Assistant Professor at University of Pennsylvania, Pearlman School of Medicine, Infectious Disease Division. Her research interests are HSV-2 vaccine development against genital herpes disease and HSV-2 HIV-2 co-infections. She has published numerous research articles and serving as an editorial board member of Journals of antivirals and anti retrovirals, Journal of Immunoassay and Immunochemistry.

Abstract:

About 500 million people are infected with Herpes Simplex Virus type 2 (HSV-2) worldwide. Genital HSV-2 infection is one of the major causes of genital ulcer disease and the risk of HIV-1 acquisition and transmission by 3-4 fold in humans. Efforts to prevent genital ulcer disease with acyclovir failed to reduce HIV-1 acquisition or transmission, supporting the need for an effective vaccine. We developed a trivalent gC2/gD2/gE2 (HSV-2 glycoprotein C, D and E) subunit vaccine that generates high levels of neutralizing antibodies, blocks HSV-2 immune evasion from complement, blocks IgG-Fc binding to the HSV-2 IgG Fc receptor, and is highly efficacious in preventing genital disease and viral shedding in guinea pigs. Here we present an immunogenicity evaluation of gC2/gD2/gE2 vaccine in macaques. Female macaques were immunized three times four weeks apart with 20g of each gC2, gD2, and gE2 glycoprotein or 20g gC2 alone with CpG and alum as adjuvants. After the third immunization, plasma analysis showed high titer antibody responses to each antigen, high titer neutralizing antibodies, and antibodies that blocked complement C3b binding to gC2 and IgG Fc binding to gE2. Six months after the third vaccination, the immune responses to each glycoprotein had declined 2-3 fold, but boosted within 2-weeks after a booster immunization administered at 9 months. Additionally we detected antigen specific antibody response in vaginal fluid. Importantly, analysis of PBMCs from macaques that were immunized with gC2 alone, showed a gC2 specific CD8 T cell response after 3 immunizations. In addition, antigen specific poly-functional CD4 T cell responses are induced in the trivalent vaccine group. Our results show that the trivalent gC2/gD2/gE2 subunit antigen vaccine generates highly potent immune responses in Rhesus macaques and may prove to be a promising genital herpes vaccine candidate for future trials in human.

Speaker
Biography:

Silvia Montaner is working as Associate Professor in Department of Oncology and Diagnostic Sciences, University of Maryland, Baltimore, USA.

Abstract:

Kaposi’s sarcoma (KS) is a vascular neoplasm caused by infection of endothelial or endothelial precursor cells with the Kaposi’s sarcoma associated herpesvirus (KSHV/HHV8). Research efforts have focused on defining the molecular events explaining how KSHV promotes pathological angiogenesis and KS tumor formation. mTOR/HIF-1 has been shown to be a fundamental pathway driving these processes through the upregulation of angiogenic and inflammatory genes, including VEGF, ANGPTL4, and ANGPT2. Interestingly, HIF-1 has also been implicated in the upregulation of metabolic genes associated with aerobic glycolysis and the growth of solid tumors. However, whether HIF-1 plays a role in regulating cell metabolism in KS remains unexplored. Here, we show that the HIF-1 metabolic effector, pyruvate kinase 2 (PKM2), is upregulated upon KSHV infection of endothelial cells and is necessary to maintain aerobic glycolysis in infected cells. We further demonstrate that PKM2 regulates KS angiogenic phenotype by acting as a coactivator of HIF-1 and increasing the levels of HIF-1 angiogenic factors, including VEGF. Indeed, inhibition of PKM2 expression blocked endothelial cell migration and differentiation of KSHV-infected cells. We also investigated whether PKM2 regulates the angiogenic dysregulation induced by the KSHV-encoded G protein-coupled receptor (vGPCR), a viral oncogene that promotes Kaposi’s sarcomagenesis through the upregulation of HIF angiogenic factors. Interestingly, we found that PKM2 controls vGPCR-induced VEGF paracrine secretion and vGPCR oncogenesis in vivo. Our findings provide a molecular mechanism for how HIF-1 dysregulation in KS fuels both angiogenesis and tumor metabolism and support further investigations on therapeutic approaches for KS targeting HIF-1 and PKM2.