Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 11th World Congress on Virology and Infectious Diseases Tokyo , Japan.

Day 1 :

Keynote Forum

Hiroshi Ohrui

Yokohama University of Pharmacy ,Japan

Keynote: A very excellent Anti-HIV modified nucleosides from design to the current results of clinical trials

Time : 10:00-10:40

Conference Series Virology Asia 2018 International Conference Keynote Speaker Hiroshi Ohrui photo
Biography:

Dr.Hiroshi Ohrui received Ph D. Degree (1971) from The University of Tokyo. He joined Riken (1966), moved  to Tohoku University (1981) and   to Yokohama University of  Pharmacy (2006). He worked for Dr. J. J. Fox at Sloan-Kettering Institute for Cancer Research (1972-1973) and Dr. J. G. Moffatt at Syntex Research (1973-1974).He received several awards including The Japan Society for Analytical Chemistry Award (2004), and Japan Academy Prize (2010).His research interests cover organic synthesis, chemical  biology  and chiral discrimination.

Abstract:

4’-C-Ethynyl-2-fluoro-2’-deoxyadenosine (EFdA) is attracting much attention due to  its extremely excellent anti-HIV activity and  physiological properties. EFdA  prevents the emergence of resistant HIV mutants,  is over 400 times more active than AZT and several orders of magnitude more active than  the other clinical reverse-transcriptase inhibitor y 2’, 3’-dideoxynucleoside drugs, very low toxic, very long acting,  and very useful for prophylaxis.EFdA is now under clinical trialsby Merck &  Co. as MK-8591.In the beginning,  a general  idea for the development of anti-viral modified nucleosides is presented, and  next,  the development of EFdA is discussed and then  the current results of the clinical trials reported by Merck will be presented.For the design of the modified nucleoside which could solve the critical problems that  the clinical drugs have (emergence of drug-resistant HIV mutants,  adverse effect by drugs, necessity to take  consirerble amount of drugs), four working hypotheses were proposed .  They are (1) the way to prevent the emergence of drug-resistant HIV mutants, (2) the way to decrease the toxicity of modified nucleosides, (3) the way to provide the modified nucleoside with stability to both enzymatic and acidic glycolysis for long acting, and (4) it is possible to develop selectively active to HIV and very low toxic to human based on the difference of the substrate selectivity between viral and human nucleic acid polymerses.4’-C-substituted-2’-deoxy nucleoside (4’SdN) was designed based on the hypotheses (1 and 3), and the additional  modification of 4’SdN was performed  based on the hypothesis (2). The details of the all  hypotheses will be discussed.To prevent the deamination of adenine by adenosine deaminase, a fluorine atom was introduced at the 2-position of adenine.Finally, EFdA, modified at the two position (2 and 4’) of the physiologic 2’-deoxyadenosine and has  extremely excellent anti-HIV activity,  was  successfully developed.

 

 

Conference Series Virology Asia 2018 International Conference Keynote Speaker Chau-Ting Yeh photo
Biography:

Dr.Chau-Ting Yeh obtained his MD from National Taiwan University and PhD from Department of molecular microbiology and immunology, University of Southern California. He is the director of Liver Research Center, Chang Gung Memorial Hospital, Taiwan, since 2007. His research interests focus on (i) HBV antiviral drug-related mutants and their oncogenic potential, and (ii) New strategies applying precision medicine to treat hepatocellular carcinoma. He has published more than 200 papers in SCI indexed journals.

 

Abstract:

Statement of the Problem: Replication of hepatitis B virus (HBV) depends on an error prone reverse transcriptase encoded by the viral polymerase gene. Mutations developed along the clinical course of chronic infection. Following widespread use of antivirals, lifelong administration of polymerase inhibitors posted a serious threat to the virus, forcing it to execute further adaptation. To date, there was no study monitoring the changes of HBV genomes over time in the post antiviral era. Methodology & Theoretical Orientation: Recently, we analyzed basal core promoter (BCP)/precore sequences in 1224 treatment-naive chronic hepatitis B patients in the post antiviral era. The prevalence of all BCP/precore mutations were compared year-on-year. Subsequently, we analyzed age-dependent correlation between BCP/precore mutations and liver cirrhosis. Findings: Overall, the prevalence of HBeAg-negative chronic hepatitis B was increasing (P < 0.001) and the patients’ age was also increasing (P = 0.001), independent of HBeAg status. Additionally, the prevalence of both G1896A and G1899A mutations was increasing (from 67.50% to 74.45% [P = 0.003] and 20.00% to 26.81% [P = 0.019], respectively). In HBeAg-positive subgroup (n = 398), only the prevalence of G1899A mutation and HBV-DNA levels were increasing yearly (from 2.50% to 17.44% [P = 0.038] and 7.74 to 8.30 Log10 copies/mL [P = 0.013]). These two factors were also independent to each other. In HBeAg-negative subgroup (n = 826), a significant decrease in the prevalence of A1752G mutation was found (P = 0.022). Subsequent study showed that the G1899A mutation was associated to liver cirrhosis development in old age patients. In fact, in patients > 65 years of age, G1899A was the only associated mutation when evaluating all BCP/ precore mutations. Conclusion & Significance: HBV continued to evolve in the post antiviral era. The prevalence of G1899A mutation was increasing, associated with liver cirrhosis in old age patients.

 

Keynote Forum

Limin Chen

Chinese Academy of Medical Sciences and University of Toronto, China

Keynote: Activation of the ubiquitin-like ISG15/USP18 signaling pathway contributes to interferon resistance of HCV and HBV

Time : 11:30-12:00

Conference Series Virology Asia 2018 International Conference Keynote Speaker Limin Chen photo
Biography:

Dr.Limin Chen,affiliate scientist with the University of Torontoa and also a professor with the Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), now is the director and chief scientific officer of the center for transfusion transmitted diseases, Institute of Blood Transfusion (IBT), CAMS/PUMC, Member of the American Association for Studies of Liver Diseases (AASLD) and Canadian Association for Studies of Liver (CASL). He obtained his MD, MSc in biochemistry and molecular biology in China, PhD in molecular genetics at the University of Toronto. Dr. Chen obtained his postdoctoral training both at the Merck Research Laboratories and at the Harvard Medical School . Currently Dr. Chen’s research focuses on the virus-host interaction of the hepatitis viruses, especially HCV and HBV.  He pioneered the work on identification of the response signature of HCV non-response to interferon treatment and proposed a novel mechanism on how HCV exploits host innate immune response to benefit its persistent infection and resistance to interferon-based therapy.

 

Abstract:

Activation of the type-I interferon (IFN) signaling pathway poses the first line of defense against many virus infections, including HCV and HBV. Our previous work identified, using high throughput gene expression profiling,  18 differentially-expressed hepatic genes between treatment responders (Rs) and non-responders (NRs) to IFN treatment of patients chronically infected with HCV. 3 out of these 18 genes are involved in the same ubiquitin-like ISG15/USP18 signaling pathway, with higher expression levels in the pre-treatment liver tissues of NRs, indicating that activation of the ISG15/USP18 signaling contributes to treatment non-response leading to persistent infection. Similar findings were observed in chronic HBV infection. Mechanistically, some of these ISGs, such as ISG15 and ISG16 stimulated HCV replication and blunted IFN anti-HCV activity. All these data point out that type-I IFN signaling is a “double-edged” sword: while activation of this pathway is indeed necessary to control viral spread, over-activation of this pathway leading to the activation of the ISG15/USP18signaling  actually benefits virus to facilitate its persistent infection.

 

Keynote Forum

Gilbert Glady

European Bio Immune(G)ene Medicine Association ,France

Keynote: BI(G)MED -Bio Immune(G)ene Medicine as an innovative nanotherapeutical immunotherapy of chronic viral reactivations related to EBV

Time : 12:00-12:30

Conference Series Virology Asia 2018 International Conference Keynote Speaker Gilbert Glady photo
Biography:

Dr.Gilbert Glady acquired during the last twenty years an expertise in immunology and immunogenetics, and also developed interest for alternative medicines, that leaded him to nanomedicine and nanobiotechnology. He thus became in 2010 the creator of the BI(G)MED method (Bio Immune(G)ene Medicine) and director of EBMA, the European association for training the medical profession in BI(G)MED. He has participated in numerous international congresses in the field of immuno-allergology, infectiology and oncology with posters and oral presentations.

 

Abstract:

The term "viral reactivation" is far from being widely accepted by the scientific community; perhaps this is due to an initial semantic misunderstanding of the notions of infection and reactivation, the second not being a particular form of the first, but something very different coming under a permanent but somehow restrained conflict existing between a latent and recurrent virus and the immune system. EBV is among all viruses the one where the concept of reactivation applies the best, with its genome being of consistent size and very adaptive, able to modulate various types of latency, to mimic the immune reactions engaged against him, to integrate into cellular DNA to controll it and ultimately immortalize the carrying cell. This viral reactivation, expression of a conflict whose outcome will long remain uncertain, will be able to generate a large number of pathological disorders, ranging from a banal chronic fatigue syndrome to malignancies, to a large number of auto-immune diseases. Once the biological diagnosis has been made, it is important to implement a treatment capable of neutralizing the aggressor and preventing him from initiating the pathophysiological processes responsible for the mentioned above disorders. This possibility exists today by resorting to a therapy using ultra low doses of various types of immunocompetent molecules, but also of epigenetic regulators such as non-coding RNAs being of viral origin or belonging to the host cell. Some clinical examples will make it possible to better specify the therapeutic procedure used and to emphasize its biological effectiveness.

 

 

  • Types of Infectious Diseases
Speaker
Biography:

Priya Madhavan obtained a basic degree in microbiology. Over the years, she has developed expertise in antimicrobial and anticancer activities from natural products, host-pathogen relationships, drug resistance in microorganisms, infectious and neglected infectious diseases and metabolic diseases. Having had experience in a various fields, she will continue to contribute her knowledge in teaching undergraduates and postgraduates. Her professional memberships include Malaysian Microbiology Society, Malaysian Society of Tropical Medicine and Parasitology, American Society of Microbiology (ASM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and International Society of Human and Animal Mycology (ISHAM). She is currently involved in the following research groups at her university, i.e. Ageing and Quality of Life, Infectious Diseases, Cancer Innovation and Metabolic Research, Experimental Medicine Research.

 

Abstract:

Statement of the Problem: The virulence of Candida species is due to repertoire of factors, specifically, the ability to form biofilms. Medical devices such as intravenous catheters, prosthetic heart valves and orthopaedic implants provide pathogenic microorganisms with a surface to adhere to form biofilm. Fungi present as biofilms are often resistant to antifungal treatment because these biofilms offer a protective barrier that prohibits the drugs to get to the drug acting sites of the fungi. The objective of this study is to investigate the architecture of the biofilms of Candida rugosa using confocal scanning laser microscopy (CSLM) and antifungal susceptibility patterns of Candida rugosa biofilm at three-time points: 24h, 48h and 72h towards fluconazole, voriconazole, itraconazole and amphotericin B. Methodology & Theoretical Orientation: CSLM was used to visualize Candida rugosa biofilms at 1.5, 6, 12, 18, 24, 48, 72 and 96 hours for two clinically isolated strains of Candida rugosa. For the antifungal susceptibility test, a total of nine clinically isolated strains of Candida rugosa were grown in RPMI-1640 medium at 37ºC at 24, 48 and 72 hours in 96 microtiters well plates. The antifungal susceptibility test was performed using a broth microdilution method according to the M27-A3 guidelines for yeasts. The biochemical quantification of Candida biofilms was performed by the 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT Assay) reduction assay. Findings: From the CLSM images, the mature Candida rugosa biofilms consisted of a dense network of yeasts cells and pseudo-hyphal elements at 24, 48 and 72 hours. Candida rugosa biofilm at all the time points were less susceptible to all the antifungal treatment and exceeded the recommended concentrations. From the antifungal susceptibility test, the biofilms are resistant to fluconazole at >64µg/mL and >16µg/mL for amphotericin B, voriconazole and itraconazole, respectively. Conclusion & Significance: In conclusion, the ability of Candida rugosa to form biofilms may attribute to the resistance towards the antifungals.

 

  • Bacterial Infection
Speaker
Biography:

Associate Professor John Miles is an NHMRC Career Development Fellow Level 2 (2017-2020) and leads Molecular Immunology at the Australian Institute of Tropical Health and Medicine, James Cook University, Cairns. He also holds adjunct Associate Professor positions at University of Queensland, Griffith University and Cardiff University. A/Prof Miles is a leader in understanding the interplay between the human immune system and infectious disease and chronic conditions. A/Prof Miles has specialist expertise researching host/pathogen interactions and deconstructing the pathomechanisms of multiple human diseases. A/Prof Miles’ research into human immune system function has been recognised through 19 awards and prizes including the Centenary Medal from Her Majesty Queen Elizabeth II for Distinguished Service to Medical Research and the Community and the 2013 Young Tall Poppy Science Award from the Federal Government & AIPS.

 

Abstract:

The increasing global incidence of non-tuberculous mycobacterial (NTM) infection is of growing concern. New evidence of person-to-person transmission of multidrug-resistant NTM adds to the global alarm. The reasons why certain individuals are at risk of these infections is unknown. Using high definition flow cytometry we studied the immune profiles of two groups of at risk NTM patients and matched controls. The first group were cystic fibrosis (CF) patients and the second group were elderly individuals. CF patients with active NTM infection or a history of NTM infection exhibited a unique surface T cell phenotype with a marked global deficiency in TNFα production. Immune-based biomarkers were determined that could identify CF individuals at risk of NTM infection with a regression model of AUC=1. In contrast, elderly individuals with NTM infection exhibited a separate T cell phenotype underlined by the high prevalence of exhaustion markers and dysregulation in type 1 cytokine release. Collectively, these data will be of significant diagnostic and prognostic value for NTM patient management and could be used to identify new therapeutic pathways and new targets to correct T cell dysfunction.

 

 

  • Neuro Virology
Speaker
Biography:

Dingjie has completed her PhD in 2009 from Institute of Microbiology, Chinese Academy of Sciences. She is the deputy director of Nanjing Center for Disease Prevention and Control. She has published more than 30 papers in reputed journals and has been serving as an reviewer for several journals.    
 

 

Abstract:

Noroviruses are the most common cause of acute gastroenteritis (AGE) worldwide, remaining a significant public health problem in both high-income countries and developing countries. In 2016/17 norovirus epidemic season, 34 out of 40 AGE clusters/ outbreaks were laboratory-conformed as GII positive, outnumbering the total number of norovirus clusters/ outbreaks in the past 3 epidemic seasons in Nanjing area. The unusual active norovirus activity and the sharp rise in the AGE outbreaks were presumably due to the predominance of an emergent genotype GII.P16/GII.2 and the concurrent circulation of several other genotypes among which GII.P7-GII.6 and GII.P22-GII.5 were rare recombinant strains. The previously predominant novel GII.P17-GII.17 came second as one of the causative genotypes. Altogether 27.5% of the norovirus outbreaks due to GII.P16-GII.2 strains occurred in kindergartens and elementary schools.The intervariant GII.4 recombinant form GII.P4_New Orleans_ 2009/ GII.4_Sydney_2012, which was considered to have the potential to become an epidemic or pandemic variant, had not been detected. In the current 2017/18 winter season, however, the circulating norovirus genotypes which have caused the majority of norovirus AGE outbreaks are GII.P16/GII.2 and GII.Pe-GII.4. In conclusion, we have observed the tendency that multiple genotypes instead of one single predominant variant have been responsible for the seasonal norovirus epidemic since GII.4 decreased its prevalence from 2014 onwards. The  novel GII.P17-GII.17 replaced GII.4 in 2014/15 winter season and the emergent GII.P16/GII.2 surpassed the  novel GII.P17-GII.17 in 2016/17 winter season. It remains unknown, however, whether the continuous emergence of novel norovirus variants capable of spreading may occur.

 

  • Research on virology and Infectious diseases

Session Introduction

Omar Bagasra

Claflin University ,Usa

Title: Sexual Transmission of Zika Virus via Spermatozoa
Speaker
Biography:

Abstract:

Study Qustion: What is the mechanism of sexual transmission of Zika Virus?

Summary Answer: By utilizing exquisite reverse-transcriptase-initiated in situ PCR (RT-in situ PCR), which enables an improved visualization of spermatozoa’s subcellular compartments; we precisely localized the mid-piece of sperm that carry receptors for Zikv.

What is already known: Zikv is transmitted sexually and recent studies have verified Zikv presence in semen of previously Zika-infected patients for more than 6-months post-infection when Zikv had disappeared from blood, saliva and urine. Strong serial analyses of various body fluids suggest that Zikv can be transmitted between sexual partners. Currently, there is limited information on the association of the virus with human semen cell types that may carry the virus.

Study design, size, duration: Analyses were carried out to localize Zikv for subcellular localization of Zikv on cell types. The Tyro3 receptor for Zikv was co-localized by dual immunocytochemistry with specific monoclonal antibodies.

Participants/Materials, setting, Methods: Three semen specimens were purchased from a commercial sperm bank. Motile sperm was separated from non-motile cells by the ‘swim up’ technique. Each of the semen fractions was infected with Zikv at the multiplicity of infection (moi) of 0.1.0 and 1.0 and evaluated for the primary targets of Zikv in the semen cells by RT-in situ PCR and confirmed by real time RT-PCR.

Main results and the role of chance: Zikv was present primarily at the mid-piece of mature spermatozoa in about 30% of the sperm. In addition, we determined that Tyro3 receptors, primarily expressed on mid-piece of human spermatozoa, play a role in Zikv binding and entry into spermatozoa, Conclusions: Our data strongly suggest a potential sexual/horizontal route of transmission for Zikv primarily via infected sperms; most likely Zikv enters the sperm via the Tyro3 receptor found at the mid-piece of the mature spermatozoa.

Limations, reasons for Caution: We are uncertain as to what phase of spermatogenesis, that in human takes about 120 days, sperms are permissive to Zikv. If permissiveness was very early during spermatogenesis males could be infectious for ~120 days after the disappearance of viremia in an infected man.

Wider Implication of the findings: Our findings bring a new focus on the current affords to develop Zikv vaccine.  Why in the presence of anti-Zikv Abs infected men are still able to transmit the virus sexually? We suggest that only certain subclass of IgG (i.e., IgG4) can cross the blood-Sertoli barrier therefore, a successful vaccine must provoke a subclass of IgG can quell Zikv inside the seminiferous tubules.

Study funding/competing interest:These studies were not funded by any governmental or private funding.  The authors declare that there are no conflicts of interest.

 

  • Molecular virology

Session Introduction

Zhongtian Qi

Second Military Medical University,China

Title: Molecular Mechanism of Japanese Encephalitis Virus Entry into Human Neuronal Cells
Speaker
Biography:

Zhongtian Qi is a full Professor of microbiology in the Department of Microbiology at the Second Military Medical University (SMMU) in Shanghai, China. He received his BS degree in medicine from SMMU in 1977, and MS degree in medical microbiology in 1981 and a PhD degree in clinical immunology in 1993 from the same University as above. He once studied in the Department of Microbiology at New York University of the US from 1986 to 1987, and then in the Department of Microbiology and Immunology at University of South Florida of the US from 1987 to 1989. He worked as a Visiting Associate Professor in the Second Internal Medicine at Kagoshima University Hospital in Japan from 1991 to 1992, and as a Visiting Senior Scholar in the Department of Pathology & Laboratory Medicine at Tulane University in the US from 2001 to 2002. His research interests focus on pathogenesis and immunity of medically important viruses, especially on hepatitis virus, Japanese encephalitis virus, and dengue virus.

 

Abstract:

Background & aim:Japanese encephalitis virus (JEV) is a neurotropic virus, which causes Japanese encephalitis (JE) in humans. The fatality rate of JE ranges from 20% to 30%, and 30%-50% of survivors are left with severe neurological sequelae. The mechanism of JEV entry into neuronal cells to establish infection remains unclear. Previous studies once showed that JEV was endocytosed into neural stem cells by a clathrin-dependent pathway. But recent work indicated that JEV infects neuronal cells through a clathrin-independent endocytic pathway. The aim of the present study is to clarify host factor involved in JEV cell entry, and to reveal molecular mechanism of JEV entry into neuronal cells.

Materials & methods:A targeted siRNA silencing screen using human endocytic/membrane trafficking library from Dharmacon was used to identify cellular factors involved in JEV entry. The siRNAs that inhibit JEV wild-type strain SA14 infection were identified in primary evaluation screening. Then, a pseudotype JEV (JEVpv) system was utilized to re-test those genes which are of inhibitory effect on JEV infection in the primary screening. Finally, specific inhibitors and dominant-negative mutants were used to examine their effect on endocytic pathways of JEV entry into neuronal cells.

Results:A total of 23 human genes with inhibitory effect on JEV infection were obtained in the primary screening. 15 out of the 23 host genes were identified as key molecules for JEV cell entry. Further studies showed that silencing 1 of the 15 genes, caveolin-1, resulted in a decrease in JEV viral entry. Silencing of dynamin-2 gene also exhibited an inhibitory effect on JEV entry. JEV entry was found to induce an increase in caveolin-1 phosphorylation. A large proportion of incoming JEV virions colocalized with caveolin-1 was observed in JEV-infected cells.

Discussion and conclusion:Caveolin-1 is a major defining marker of caveolae, and the crucial driver for caveolae formation. Dynamin-2 is a large GTPase which mediates the release of newly formed endocytic vesicles from the plasma membrane. Our data demonstrate that JEV takes advantage of caveolin-1 and dynamin-2 to establish its infection in neuronal cells. The findings might help better understand the JEV-host interaction, and provide with the possibility for design of novel anti-JEV agents.