Day 1 :
University of Minnesota Medical School, USA
Time : 10:00 - 10:50
Irina St. Louis has completed her MD and Ph.D. degrees from Ural State Medical Academy, Russia. She has completed her Residency in Laboratory Pathology from Russian Medical Academy for Postgraduate Education, Moscow. She has joined the Department of Microbiology, at the University of Minnesota, as a Postdoctoral trainee, followed by Fellowships at the University of Minnesota Super computing Institute and Lymphoma Research Foundation. She has worked as an Assistant Professor at the Department of Medicine. Her current clinical project focuses on the identification of molecular biomarkers for immune restoration diseases. She is engaged in many clinical studies, within the Global Health and International Medicine Program. These studies involve the stratification of AIDS patients, for optimal therapies and examining the immunopathogenesis of immune restoration disorders, with an emphasis on defining the activation, maturation, and regulation of the immune cell subsets involved. The studies also include searches for biomarkers of Immune Reconstitution Inflammatory Syndrome (IRIS).
Introduction & Aim: Paradoxical Cryptococcosis- associated immune reconstitution inflammatory syndrome (C-IRIS) occurs in 20% of HIV-infected patients with Cryptococcal Meningitis (CM) after they commence Antiretro Viral Therapy (ART). The pathogenesis of C-IRIS remains poorly understood, with few biomarkers to predict C-IRIS or to establish an early diagnosis. We investigated periferal blood transcriptomic profiles of ART-naive, advanced stage HIV-infected subjects with confirmed cryptococcal meningitis, in two recently completed clinical trials: Immune Restoration Disorders (IRD) and Cryptococcal Optimal ART Timing (COAT). The aims of presented research are to (1) Identify a dysregulation in gene expression underlying C-IRIS (2) Identify novel diagnostic or predictive transcriptomic biomarkers associated with the development of C-IRIS or death due to C-IRIS.
Method: C-IRIS subjects were compared with controls, matched by age, gender, baseline HIV viral load, and CD4+ T-cell counts. Subjects were assigned into 4 groups (1) No C-IRIS or death (controls, appropriate immune restoration) (2) C-IRIS survivors (3) C-IRIS death and (4) Death but no C-IRIS (other causes). Gene expression was analized longitudinally, by whole genome microarrays or next-generation sequencing, over 12 weeks on ART (at 0 (baseline), 2, 4, 8, 12 weeks after ART initiation).
Result: The predictor screening algorithms identified the low expression of interferon-driven anti-viral defense pathway components such as interferon-inducible genes and higher expression of transcripts that encode for granulocyte-dependent pro-inflammatory response molecules as predictive biomarkers of subsequent C-IRIS at baseline. Subjects who developed early C-IRIS (occurred within 12 weeks of ART initiation) were characterized by upregulation of biomarker transcripts involved in innate immunity such as the inflammasome pathway while those with late C-IRIS events (occurs after 12 weeks of ART) were characterized by abnormal upregulation of transcripts expressed in T, B and NK cells, such as IFNG, C1QC, IL27 and others. The AIM2, HLA-DQA2 and BEX1 were identified as novel biomarkers for both early and late C-IRIS events. Majority of biomarker transcripts involved in innate immunity (inflammasome and toll-like receptor signaling), were upregulated to even higher levels in the C-IRIS death group. In addition, the upregulation of transcripts encoding components of IL6, B-cell signaling, and Fc-gamma receptor-mediated phagocytosis were associated with death in those with C-IRIS. Patients from the death but no C-IRIS group showed significant activation of NFkB and death receptor pathways at baseline and strong signature of neutrophil activation/degranulation at 2 weeks on ART.
Conclusion: Low levels of transcripts encoding components of interferon-driven antiviral immune responses prior to ART was predictive of the development of C-IRIS. Fatal C-IRIS events exhibited exaggerated inflammation, represented by upregulation of transcripts encoding components of both adaptive (B-cell) and innate immunity. Although each type of C-IRIS events have seemingly similar clinical manifestations, they have different molecular phenotypes and are driven by contrasting inflammatory signaling cascades. These results provide insight into the pathogenesis of C-IRIS that could be applied to developing diagnostic tests or targeted immunomodulatory treatments.
- Plant and Animal Virology
Location: Furama RiverFront
University of Veterinary and Animal Sciences, Pakistan
Sohail Raza is working as an Assistant Professor, Department of Microbiology, UVAS Lahore. He is also serving as an Institutional Bio-safety officer of the university. During Ph.D., he has worked on the construction of gene-deleted marker vaccine against Bovine Herpesvirus 1 and mechanism involved in the viral maturation and egress. Due to his contribution in this area, he has been awarded as the Distinguished Research Scholar Award, Excellent Research Contribution Award and Outstanding Research Thesis Award from the government of China. He has published 07 papers in impact factor International Journals. His research focuses on the development of recombinant vaccines using trans-disciplinary approaches against prevalent diseases in Pakistan.
Bovine Herpes Virus 1 (BoHV-1) is an important pathogen of cattle and buffalo, it leads to significant economic losses to the dairy and beef industry. BoHV-1 DNA replication takes place in the nucleus of infected cells. The process is mediated by a number of proteins, including a virus-encoded DNA polymerase holoenzyme complex, which consists of the catalytic subunit pUL30 and its processivity factor pUL42. In this study, we characterized the UL30 and UL42 proteins of BoHV-1 in transfected cells. A bioinformatics analysis identified a putative classical Nuclear Localization Signal (NLS) located at the C-terminus of pUL42 (residues 379-378), but no similar signals where identified on pUL30. To confirm this, differently tagged UL42 and UL30 fusion proteins had been expressed in MDBK cells. The co-immunoprecipitation and immunofluorescence experiments had been performed. The Co-immunoprecipitation of differently tagged UL42 and UL30 fusion proteins demonstrated that both proteins interact with each other even in the absence of other viral proteins. Importantly, when individually expressed in the absence of other viral proteins, pUL42 localized to the cell nucleus, whereas pUL30 was retained in the cytoplasm. Upon co-expression, both proteins had been localized in the nucleus. Overall our results are consistent with the hypothesis that during BoHV-1 infection UL42 transports the catalytic subunit into the nucleus, similarly to what reported for other Herpes viridae members.
- Deadly Viral Diseases
Location: Furama RiverFront
Indian Institute of Science Education and Research, Mohali,India
Indranil Banerjee is currently working as an Assistant Professor at IISER Mohali, India. He has completed his Ph.D. from Institute of Biochemistry, Swiss Federal Institute of Technology (ETH Zurich), Switzerland and his Postdoctoral Fellow at Friedrich Miescher Institute (FMI Basel) and Novartis Institutes for Biomedical Research (NIBR), Switzerland. In 2016 he won Pfizer prize for his research in immunology and infectious diseases. He published many papers in reputed journals and his area of research includes understanding the core of influenza and dengue viruses and their treatment.
Viruses are masters of camouflage and deception despite being extremely simple in structure and composition. Devoid of any means of independent locomotion, they disseminate by exploiting cells and organisms. A critical moment occurs when a virus particle reaches a potential host cell and attaches itself to the surface. It must now deliver its genome and accessory proteins into the host cell for replication. Unable to gain access to the cell on their own, viruses have evolved elegant strategies to extract assistance from the host cell for their entry and genome release. Influenza virus, one of the most devastating human pathogens, uses a unique trick to get its capsid unpacked within the host cell. It mimics misfolded protein aggregates by carrying unanchored ubiquitin chains and thereby activates the ubiquitin- and HDAC6-dependent protein degradation machinery (aggresome) of the cell. Upon activation, diverse components of the aggresome processing machinery including the microtubule- and actin-associated molecular motors dynein, dynactin and myosin 10, generate physical forces to crack open the viral capsid and release the viral RNA genome into the cytosol for replication. This cytoskeleton motor-assisted capsid disassembly program not only provides yet another interesting insight on how viruses manipulate the host cells to propagate but also offers potential targets such as myosin 10, dynein and HDAC6 for new antiviral strategies to combat this deadly virus.
King Edward Medical College, Pakistan
Somia Iqtadar has completed her MBBS from King Edward Medical University, Pakistan. She has completed her Post graduation degree from Fellow of College of Physicians and Surgeons Pakistan. She currently practicing Internal Medicine at Race View Hospital, Lahore and CardioMed Clinic, Lahore. She has published many research papers in the reputed journals and her main research interest includes internal medicine, infectious diseases, cardiovascular medicine and metabolic disorders.
Background & Aim: Dengue is a mosquito-borne tropical disease caused by Dengue virus. Dengue can range from asymptomatic infection to a more severe form of dengue hemorrhagic fever with sometimes failure of circulatory system leading Dengue Shock Syndrome. Calcium, an important serum electrolyte, plays a pivotal role in cardiac and circulatory functions. Due to the paucity of local data, we conducted this study to see the association of hypocalcemia with the severity of dengue fever in our local population. The study aims to find the association of hypocalcemia in patients of Dengue fever with and/or without DHF. The study design was based on the cross-sectional study. Place and duration of the study was at medical wards of Mayo Hospital, Lahore, from 05-01-2018 to 05-07-2018.
Method: Patients with dengue fever were included in the study. Daily CBC was done and the presence or absence DHF was noted. Blood samples for serum calcium and serum albumin levels were drawn. Corrected calcium levels were calculated. Data was entered in SPSS 20. Presence of hypocalcemia was compared in patients with and without DHF.
Result: A total of 80 patients were included in the study out of which 45 (56.25%) were males and 35 (43.75%) were females. The mean age of patients was 33.59±14.33 years. 34 (42.5%) patients had DHF while 46 (57.5%) patients with dengue did not develop DHF. Out of 80, 23 (28.75%) patients had hypocalcemia. In patients with DHF, hypocalcemia was present in 18 (52.9%) cases while only 5 (10.9%) patients who did not have DHF developed hypocalcemia. This difference was significant (p<0.05).
Conclusion: Hypocalcemia is significantly higher in patients with DHF and can be used as an early predictor for complications and severity of the disease.