Day 2 :
- Track 7: Therapeutic Approaches and Targets for Viral Infections
Universiti Putra Malaysia, Malaysia
Title: Evaluation of antiviral properties of edible bird nest (EBN) extracts on Influenza A virus (IAV) attenuation
Time : 11:55-12:15
Parvaneh Mehrbod started her postgraduate study in 2008 in University of Tehran, Iran, in the field of Cellular and Molecular Biology followed by PhD study in Molecular Biotechnology in Universiti Putra Malaysia (UPM) in 2013 and currently she is doing her postdoctoral study in UPM. During her study, she actively involved and participated in national and international conferences, workshops and seminars. She has published some of her research findings in peer reviewed journals and conference proceedings, and has many more under writing and revising.
Influenza infection is still a high risk disease affecting human and different species of animals by causative agent influenza A virus (IAV). Currently there is neither effective vaccine nor efficient drug to dominate this infection. Edible Bird Nest (EBN) as a popular traditional Chinese medicine (TCM) is believed to have health enhancing effects such as anti-tumor activity, anti-viral and immunoenhancing effects. The aim of this study was to highlight inhibitory effects of EBN extract on IAV infection. Firstly, two types of EBN samples were collected from two different parts of Malaysia and prepared in the forms of filtrate and substrate extracts with 2 different enzymes treatments based on the established methods with modification. Then, the cells were treated with effective concentration (EC50) of EBN extracts in combined treatments with influenza A viruses in different exposure types (co-, pre- & post-penetration treatments). Using MTT assay and Heamgglutination assay (HA), the cell viability and the viral titers were examined, respectively. The effects of combined treatments on the cytoskeleton structure of the cells were also illustrated using rhodamine staining. The results demonstrated that EBN extracts in combined treatments with influenza A viruses significantly reduced the virus titer and increased the cell viability especially in post-penetration treatments (p≤0.05) as compared to the virus inoculation without EBN treatment. In addition, the interaction amongst different types of EBNs, exposure types and strains of the viruses showed significant main effect on cell viability variance (P<0.05). EBN treatments showed a moderating effect on the actin filaments polymerization affected by the virus inoculation. In conclusion, EBN has the capacity to be introduced as an alternative or supplementary medicine to other chemical drugs in upcoming pandemics.
University of Texas, Austin
Time : 12:35-12:55
Chris Sullivan received his PhD from the University of Pittsburgh and conducted postdoctoral training at the University of California at San Francisco. He is an Associate Professor at the University of Texas at Austin where his lab focuses on understanding the role of noncoding RNAs in the regulation of virus infection and the antiviral host response. He serves on the editorial boards of prestigious virology journals, has published over 40 articles in reputed journals and has received a Burroughs Wellcome Investigator of Infectious Disease Award, an NSF Career Award and was named a Kavli Fellow.
RNA interference (RNAi) has generated much excitement as a mechanism of gene regulation and as a laboratory tool for experimental gene silencing. In plants and insects, RNAi is a primary antiviral defense response, recognizing harmful nucleic acid and silencing its expression. In mammals, there are conflicting views as to whether RNAi represents a meaningful antiviral defense. In this work, we present data that address the role of RNAi in cultured mammalian cells. Specifically, we probe the interactions of host and viral RNAi machinery and/or effectors during infection. Our results uncover unanticipated activities of the RNAi machinery that strongly suggest that RNAi is not an antiviral response in at least some types of mammalian cells. On the contrary, some mammalian viruses, including members of the herpesviruses, polyomaviruses, retroviruses and anelloviruses have evolved the ability to purposely engage the host RNAi machinery via microRNAs. An emerging model is that diverse viruses utilize both host and viral miRNAs to optimize persistent infections.
Public Health England, UK
Time : 14:55-15:15
Dowall SD joined the research division of Public Health England (PHE) starting in the HIV vaccine research group that used the SIV model in rhesus macaques. During 2004, he transferred these skills to a group set up to establish the non-human primate model of TB. With a keen interest in virology and in vivo modelling, Stuart moved to the Virology and Pathogenesis research group in 2009. Within this group he has established immunological assays with viruses, and has undertaken work at Containment Level 4, primarily with Ebola and Crimean-Congo Haemorrhagic Fever (CCHF) viruses. He is Project Team Leader for multiple projects within the group studying arboviruses, haemorrhagic fever viruses and vaccines/therapeutic interventions against these pathogens.
Crimean-Congo Haemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. Between 15-70% of reported cases are fatal. There is no approved vaccine available and preclinical protection in vivo by an experimental vaccine has not been demonstrated previously. PHE scientists have developed a recombinant candidate vaccine expressing the CCHF virus glycoproteins in an attenuated poxvirus vector, Modified Vaccinia virus Ankara. Cellular and humoral immunogenicity was confirmed in two mouse strains, including type I interferon receptor knockout mice, which are susceptible to CCHF disease. This vaccine protected all recipient animals from lethal disease in a challenge model adapted to represent infection via a tick bite. Histopathology and viral load analysis of protected animals confirmed that they had been exposed to challenge virus, even though they did not exhibit clinical signs. This is the first demonstration of efficacy of a CCHF vaccine.
Universidade Federal de Alfenas, Brazil
Title: Evaluation of tetravalent and conserved synthetic peptides vaccines derived from Dengue virus Envelope domain I and II
Time : 14:35-14:55
Marcilio Jorge Fumagalli is working as a researcher in Universidade Federal de Alfenas, Brazil.
Dengue is a major worldwide public health problem, especially in the tropical and subtropical regions of the world. Primary infection with a single Dengue virus (DENV) serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing a secondary infection with a different serotype progress to the severe form of the disease, called dengue hemorrhagic fever. In this study, the vaccine potential of three tetravalent and conserved synthetic peptides derived from DENV envelope domain I (named Pep01) and II (named Pep02 and Pep03) was evaluated. Human dengue IgM/IgG positive serum (n = 16) showed reactivity against Pep01, Pep02 and Pep03 in different degrees. Mice immunization experiments showed that these peptides were able to induce a humoral response characterized by antibodies with low neutralizing activity. The spleen cells derived from mice immunized with the peptides showed a significant cytotoxic activity (only for Pep02 and Pep03), a high expression of IL-10 (P < 0.01) and a reduced expression of TNF-α and IFN-gamma (P < 0.001) compared to DENV-1 infected splenocytes. Thus these peptides, and specially the Pep03, can induce a humoral response characterized by antibodies with low neutralizing activities and probably a T cell response that could be beneficial to induce an effective immune response against all DENV serotypes and do not contributed to the immunopathogenesis. However, further studies in peptide sequence will be required to induce the production of neutralizing antibodies against all four DENV serotypes and also to improve immunogenicity of these peptides.
Medical University of Vienna, Austria
Title: Effectiveness and immunogenicity of pneumococcal vaccination in splenectomized and functionally asplenic patients
Time : 13:15-13:35
Stephanie Plefkagraduated from Medical University of Vienna in 2011 at the age of 25 years. Her research project focused on pneumococcal vaccination in splenectomized patients and was operated at the Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine at the Medical University of Vienna. Since 2012 she works as a doctor in training to become a General Practitioner at the Hospital Wilhelminenspital in Vienna.
The purposeofthisstudy was toinvestigate the effectiveness of pneumococcal vaccination, using the 23-valent pneumococcalpolysaccaride vaccine(PPV23) and/orthe 7-valent pneumococcalconjugate vaccine (PCV7), in preventing over whelming post-splenectomyinfection (OPSI) among adult asplenicpatients and patients after splenectomy. Between 1996 and 2009 145 splenectomizedand 2 functionallyasplenicpatientsreceivedeitheroneorbothvaccinations. The maincause of death in 68% oft the 53 patientswhodied was theunderlyinghaemato-oncologicaldisease, followedbysepticshock in 13.2%. In the 94 patientswhowere still aliveafter thisperiod, twelvesufferedfrom post-vaccinecomplications: pneumonia in 9 patients, otitismedia in 2, pneumococcalsepsis in 4. Splenectomizedpatientsvaccinated in thepreviousfiveyears (n=15) showedsignificantlyhigher GMCs (P<0.05) againstserotypes 4,6B,9V,14,18C,19Fand 23F thanthe non-splenectomized non-vaccinatedcontrolgroup (n=34). Patientsvaccinated in thefirst 5 years after splenectomyby PCV7 had strong serologicalresponses. Postvaccinal complications occurred in less than 10% after immunisation, but post-vaccine pneumococcal sepsis was still diagnosed in 3.3% of the splenectomised patients still alive in 2009.
University of Navarra Spain.
Title: Adeno-associated virus vectors expressing IFN-β induction pathway activating elements as alternative torecombinant IFN-β antiviral refractory treatments
Time : 10:55-11:15
Detection of pathogens by cells is a key event of defense against infections. RIG-I like receptors (RLRs) detect specific RNAs produced by virus replication and activate a signaling cascadethat results in the production of interferon beta (IFN-β) as well as several other antiviral and proinflammatory cytokines. Conventional type I IFN antiviral treatments are based on administration of recombinant purified protein or administration of different vectors that can produce type IIFN. Despite its proven antiviral and antitumoral effects, many individuals do not respond to administration of such therapies. We hypothesize that triggering of RLR pathways instead of direct IFN administration is a valid alternative for the induction of antiviral, antiproliferative and proinflammatory genes. We have developed adeno-associated virus (AAV) vectors expressing different elements of the RLR dependent pathway. Some constructs lead to an efficient IFN-β induction in a broad spectrum of cells from different species.Those vectors have been tested for their abilityto induce IFN-β, creating an antiviral state in different in vitro and in vivomodels, even in a scenario that is not responding to recombinant IFN-β. Some of AAV vectorscan synergize with the host immune system and combat viral infections. We propose the useof our strategy as an alternative to malignancies that are refractory to such type I IFN treatment like some IFN-treated resistant chronic viral infections.
Trellis Bioscience USA.
Time : 11:15-11:35
Larry Kauvar, PhD is an entrepreneur and scientist who founded Trellis Bioscience where he serves as Senior VP, Chief Scientific Officer. He was previously the founder and Chief Scientific Officer of Telik, a development stage small molecule drug company focused on oncology, and is a co-founder of Promedior, a development stage biologics company focused on fibrosis. He holds >40 US patents for drug discovery methods and tools as well as multiple specific compounds. He is one of the inventors of CellSpot™, Trellis' core technology for discovery of native human monoclonal antibodies. Dr. Kauvar received his undergraduate degree in mathematics from Harvard in 1973, his PhD from Yale in Molecular Biophysics and Biochemistry in 1978, and conducted postdoctoral research at Caltech and UC San Francisco before founding Telik
The native human antibody repertoire has long been recognized as an attractive source of therapeutics, particularly for infectious diseases. In the past, however, it has been a difficult source to exploit due to the limited lifetime of human B-cells ex vivo. Trellis has developed a microscopy based assay platform that overcomes the prior limitations and further adds multiplexing into the primary assay. Superlative antibodies have thereby been discovered for influenza, RSV and CMV. These mAbs are all high affinity (sub-nM) and broadly neutralizing across all clinical strains. Moreover, they have low toxicity risk arising from reactivity to human antigens, and are generally easy to express as recombinant proteins. Coupled to rapid manufacturing technologies under development by others, this platform may allow recovery and scale up of countermeasures to emerging pathogens in a time frame suitable to stop an epidemic
Time : 10:20-10:40
"Franco Lori (M.D.) founded ViroStatics srl in 2005, serving as President and Chief Executive Officer. After his scientific training at the Pavia CNR, Italy, (molecular biology) and NIH, USA (virology, immunology), he has accumulated experience in investigative preclinical and clinical research and drug development interacting with an extensive network in the US and Europe. With 20 years of extensive experience in Biotech management. He has overseen the successful start-up of three biotechnology companies. In 2000, he was awarded ""Hero in Medicine"" for his achievements in HIV therapy by the International Association of Providers of AIDS Care"
Viruses are intracellular parasites which carry a limited set of genetic information and therefore are completely dependent on the host cells they infect to propagate and survive. While antivirals have traditionally been designed to directly target viral proteins in search for specificity and good therapeutic indices, some virus-targeted drugs have been plagued with issues of toxicity that have severely limited their ability to be developed and utilized as therapeutics. Moreover, a common drawback for all such direct-acting antivirals is the emergence of resistance, resulting from rapid mutations of viral proteins. An alternative approach to the direct-acting antivirals is to target the key cellular proteins that are essential for viral replication and survival. This approach helps to address the issue of resistance since cellular proteins are less prone to mutate than virally encoded ones. The perception that toxicity is an issue when targeting cellular factors is a misconception. In reality, the majority of drugs used in the past and in current medical treatments target cellular mechanisms. Significantly, these drugs have been used safely and efficaciously on millions of individuals, and many drugs targeting cellular factors can be safely used chronically, often for decades (e.g. anti-hypertensive, anti-cholesterol, etc.), a distinct advantage for the treatment of chronic viral infections. Given the above, at ViroStatics we have focused our efforts on developing a new class of drugs that target viruses through the inhibition of host cellular factors. In this regard, we are pursuing the novel approach of targeting the cellular kinase CDK9 (Cyclin-Dependent Kinase 9), which is known to play an essential role for viral replication and survival in a number of infections, including HIV, EBV, HSV and HPV. While there is a broad applicability to this approach, our initial focus has been on the indication for HIV/AIDS. We are developing first-in-class Transcription Inhibitors designed to attack the unexploited, post-integration phases of HIV replication through CDK9 inhibition. HIV/AIDS offers a natural proof of concept in support to this notion: Elite Controllers, a low percentage of untreated HIV infected individuals with an undetectable HIV RNA load, exhibit an intrinsic inhibition of CDK9 activity which occurs without any apparent safety issues or the induction of viral resistance. ViroStatics’ compounds are designed to mimic this Elite Controllers’ phenotype, in essence, to pharmacologically induce “elite control” that rarely occurs naturally. Some ViroStatics’ CDK9 inhibitors suppress HPV replication in vitro with an antiviral potency up to a thousand-fold higher than the reference control drug Cidofovir. Initial screening has shown good druggability and safety profiles of CDK9 inhibitors both in vitro and in vivo. The absolute dependence of any virus on the host cellular machinery for propagation and survival represents the Achilles’ heel for all viruses. Developing cell-targeted drugs as an alternative to virus-targeted drugs would provide a new generation of antivirals that addresses the continued unmet need of drug resistance and offers the potential for new medicines for infections that cannot be presently treated.
Laboratory of Viral Diseases NIAID National Institutes of Health USA
Time : 12:15-12:35
Barna Dey is working as Staff Scientist, National Institutes of Health, USA.Her research interest is Virology, Immunology, protein science, cell biology.
Major research efforts are currently underway to achieve ‘functional cure’ of HIV whereby virus suppression is maintained in the absence of antiretroviral therapy. Cell-based therapiesare gaining momentum as a testable approach in this front. Following the clinical success of adoptive transfer of chimeric antigen-receptor (CAR)-modified T cells as a treatment for hematological cancers, we designed three CAR constructs with identical transmembranedomain and intracellular signaling domains linked to differentextracellular antigen-binding moietieswhich target highly conserved receptor-binding sites on HIV Env. The extracellular targeting moieties are derivatives of the primary receptor CD4,either alone (CD4 CAR) or attached to the 17b scFv (targeting the coreceptor binding site) via a long linker (35 aa; CD4-35-17b) or a short linker (10 aa; CD4-10-17b).Our previous studies indicated that the corresponding soluble bifunctional protein with a long linker (CD4-35-17b) neutralized HIV with extreme potency and breadth, presumably due to simultaneous binding of both CD4 and 17b moieties to the same gp120 subunit; a protein with a linker too short for simultaneous binding (as in CD4-10-17b) showed weak potency. We compared the 3 CAR constructs to test alternative concepts on the relationships between molecular binding affinity and target cell killing potency. In our in vitro studies, peripheral blood CD8+ T cellstransduced with each CAR secreted IFN-γ upon Env engagement and killed Env+ target cells.Importantly, for the suppression of HIV-1 infection of PBMCs, the CD4-10-17b CAR showed highest potency, followed by the CD4-CAR and the CD4-35-17b CAR being less effective. This result supports a model whereby cell killing is optimal when the effector/target affinity is sufficiently low to enable serial triggering, as presumably is the case for the CD4-10-17b CAR. We also noted that the CD4 CAR rendered CCR5+ cells susceptible to HIV infection, an undesired activity not observed witheither of the CD4-17b CARs. Thus the novel CD4-10-17b CAR offers superior potency without the potentially deleterious effect of the CD4 CAR, for durable targeted cell killing to achieve a functional cure.
- Track 8: Viral Hepatitis
Peking University, China
Title: The development of chronic Hepatitis in rabbits experimentally infected with Hepatitis E virus isolate from rabbit
Time : 15:55-16:15
Ling Wang completed her Ph D at Kyoto University, Japan. She is a professor of the Department of Microbiology, School of Basic Medical Sciences, Peking University, Beijing, China. She has published more than 20 papers in reputed journals on HEV research.
Under experimental conditions, rabbit HEV has been shown to be able to cross-species infect monkeys and pigs. Swine HEV isolates were also able to infect rabbits, indicating rabbits may serve as a non-primate small animal model for HEV infection. However, the pathogenesis profile of HEV infection of rabbits has not been clearly defined. This study focused on investigating the pathogenesis in rabbits following infection with a homologous rabbit HEV isolate and comparing it to that seen following infection with a heterologous swine genotype 4 HEV isolate. Three of the four animals inoculated with the homologous rabbit HEV became infected, exhibiting an intermittent viremia, obvious fluctuations of liver function biomarkers ALT and AST, and persistent fecal virus shedding throughout the nine month study. In addition, liver histopathology showed both chronic inflammation and some degree of fibrosis. Both positive and negative-stranded HEV RNA and HEV antigen were detected in liver, brain, stomach, duodenum and kidney from the necropsied rabbits. Inflammation of extrahepatic tissue was also observed. Three of the four rabbits inoculated with the heterologous genotype 4 swine HEV also became infected, showing similar levels of anti-HEV antibody to that generated following infection with the homologous virus isolate. The duration of both viremia and fecal shedding of virus was however shorter following infection with the heterologous virus and there was no significant elevation of liver function biomarkers. These results suggest that rabbit HEV infection may cause more severe hepatitis and prolong the course of the disease, with a possible chronic trend of hepatitis in rabbits.
Oregon State University USA
Title: The Original Calicivrus: An Emergent Human Pathogen Implicated on Three Continents in the Occurrence of Severe Disease Including Hepatitis
Time : 16:30-16:50
Dr. Smith received his DVM from the School of Veterinary Medicine, Washington State University, MS and Diplomat status with the American College of Laboratory Animal Medicine at Texas A & M University and the US Air Force School of Aerospace Medicine. His PhD is from the University of California Berkeley. He served 22 years in the US Air Force 11 of which were on loan to the Office of Naval Research to study Ocean Zoonoses. He has established and headed-up “Laboratories for Calicivirus Studies” at the Naval Biosciences Laboratory, Naval Ocean Systems Center/San Diego Zoo and Oregon State University. He served on and chaired the American Veterinary Medical Association’s Counsel on Research and has been a decades-long member of theCalicivius Study Group for the International Committee on Taxonomy of Viruses. Dr. Smith is a Professor Emeritus at Oregon State University, sole owner of Calicitech International LLC and the US Patent “Diagnosis, Prevention and Treatment of Calicivirus Infection In Humans”, which is the seminal patent addressing human vesiviral infection and disease.
Eighty-two years ago (1932) in Orange County California, USA,the first Calicivruswas discovered. That virus, named VesicularExanthema of Swine Virus (VESV), was species specific for domestic swine anddesignated a foreign animal disease agent, then eradicated and classified a Picornavirus. But, negative-stain electron microscopy revealed that VESV was a new virus with 32 calices (cups) in the capsid leading to the name“Calicivirus”. This group is now organized intothe family Caliciviridae having five genera;Norovirus, Sapovirus, Lagovirus, Nebovirus and theVesivirus. Two Vesivirus species arefelinecalicivirus, and the original calicivirus,VESV.Only genusVesivirus has been routinely propagatedin-vitro. Since 1972 the knownhost range for VESV expanded to include feral swine, fish, shellfish,reptiles,and marine mammals. VESV was not eradicated and by 1990,was a proven pathogen of cattle, five species of primates and humans.Throughout this host-range, vesicular disease was uncommon. Instead,VESVdisplayed a diversity of tissue trophisms. Hepatitis, myocarditis, encephalitis, pancreatitis, pneumonia, spontaneous miscarriage, hemorrhagic/DIC syndrome, diarrhea and a highly significant rise in serum transaminase levels were associated with VESV presence and/or anti-vesiviral antibodies.Human sera from three Continents werevesivirus antibody positive for association between blood transfusions and conditions causing elevated transaminases including non A-E hepatitis (P=.001). Food, water and sea-foods are probable sources of exposure and the human blood supply has shown VESV contamination.Studies find anti-VESV antibody presence in blood cleared for transfusions and some of these units have beenvesiviremic.
King Faisal Specialist Hospital and Research Center, Saudi Arabia
Title: Correlation between genetic variations and serum level of interleukin 28B with virus genotypes and disease progression in chronic hepatitis C virus infection
Time : 15:15-15:35
Mohammed N. Al-Ahdal (a Bio-Pharmacist) has completed his Ph.D. in Microbiology and Immunology from the State University of New York at Buffalo in 1985. He is the now the Chairman of the Department of Infection and Immunity at King Faisal Specialist Hospital and Research Center in Riyadh, Saudi Arabia, where he is also a Principal Scientist. He is a Professor of Microbiology and Immunology at the College of Medicine of Alfaisal University in Riyadh, Saudi Arabia and an Adjunct Professor at Sassari University in Italy and at Brunel University in the U.K. He has published more than 105 papers in reputed journals and serving as an editorial board member of some scientific journals
Hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide. Recent studies have demonstrated polymorphisms near the interleukin 28B (IL-28B) gene could predict the response to Peg-IFN-a/RBV combination therapy in HCV-infected patients. The aim of the study was to correlate the serum level of IL28B in HCV-infected patients with virus genotype/subgenotype and disease progression. IL28B Serum level was detected using IL28B-specific ELISA kit. Variations at five single nucleotide polymorphisms (SNPs) (rs8105790, rs8099917, rs7248668, rs12980275 and rs12979860) in IL28B gene region were studied and they were found to be strongly associated with HCV infection when healthy control group was compared to HCV-infected patients with all p values <0.0001. Functional analysis revealed that subjects carrying rs8099917-GG genotype had higher serum level of IL28B than those with GT or TT genotypes (p = 0.04). Also, patients who were presented with cirrhosis (Cirr) only or with cirrhosis plus hepatocellular carcinoma (Cirr+HCC) had higher levels of serum IL28B when compared to chronic HCV-infected patients (P=0.005 and 0.003, respectively). No significant association was found when serum levels of IL28B were compared to virus genotypes/subgenotypes. In conclusion, this study indicates that variation at SNP rs8099917 could predict the concentration serum levels of IL28B in HCV-infected patients. Furthermore, IL28B serum level might be useful as a marker for the development and progression of HCV-associated diseases.
National Institute for Communicable Diseases, South Africa
Time : 16:50-17:10
Nishi Prabdial-Sing is working as researcher in National Institute for Communicable Diseases, South Africa.
Around 1 million South Africans are infected with Hepatitis C virus. Most individuals remain undiagnosed until symptoms occur and, therefore, usually present with late stage liver disease. The standard of care (SOC) for treating hepatitis C in South Africa is combination therapy with pegylated interferon and ribavirin. However, not all South Africans have access to (or are able to benefit from) therapy due to high costs, poor adherence, adverse side effects and advanced stage of disease. HCV genotypes and/or mutations in the core/ non-structural regions have been associated with response to therapy and/or disease progression. Although the major genotype in South Africa is genotype 5a, studies using clinical cohorts confirm that other local genotype frequencies are increasing due to population migration and travel. This retrospective study describes (1) changing genotype frequencies within a South African high-risk clinical patient group as well as a low risk (asymptomatic) cohort of blood donors bled between the years 2008-2012and (2) molecularly characterize the core and NS5B regions of all pre-treatment samples. Methods: Sera samples from hospitals around South Africa (N=865) and from the South African Blood Services (SANBS, N=206) were analyzed quantitatively by real-time PCR and genotyped using the Versant LiPA assay. Mutational analyses were performed for selected genotype 5a samples as follows: Thirty-one samples were sequenced directly in the core region (patients N=21 and blood donors N=10) while retrospective data from 43, previously sequenced, patient samples was analyzed in the NS5B region. Mutations were identified using Mega 6.0. Sequences were compared to GenBank references for amino acids 1-318 of core and E1 and amino acids 2661-2728 of NS5B. Sequence variability was examined for known CD4+ and CD8+ T-cell epitopes and their predicted binding to HLA types known to be prevalent in the South African population determined using IEDB. Results: Genotype 5a (35.83%) was the major genotype in the patient cohort whilst genotype 1 (33.98%), was found to predominate in the blood donors. An increase in genotypes 3 and 4 was noted over the 5 year study period in both cohorts. The core;R70Q mutation (associated with poor response to pegylated interferon and ribavirin therapy in genotype 1b patients and progression to HCC) was identified in 20/21 patient samples with genotype 5a and 9 of 10 genotype 5a blood donor samples. The NS5B:S282T mutation (associated with resistance) was not seen at baseline in any of the genotype 5a samples studied. Six of the 9 known HLA-A02 restricted epitope sequences showed high-intermediate cross-reactivity (binding scores of <300 IC50nM) to two of the most common alleles present in the South African population. No known CD8+ T-cell epitopes were mapped to the sequenced NS5B region. Discussion: The study highlights the need for ongoing genotyping surveillance of HCV in South Africa to monitor changing frequencies and their impact on health care costs and burden of disease. It also broadens our knowledge and provides new insight into the diversity of HCV in pre-treatment samples belonging to the poorly studied genotype 5a which predominates in South Africa.
- Track 9: Viral Immunology
Military Health Sciences, Czech Republic
Title: Differential effects of in-vitro and in-vivo virus infection on Akt signalling in CD4+ T cells
Time : 17:10-17:30
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 workedat 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.
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. Conversely, there are viruses like varicella-zoster virus (VZV), which are not typically associated with infection of lymphocytes. However, the in vitro analysis shows, that VZV is capable of infecting CD4+ T cells at rates depending on the individual isolates and that the frequency of apoptotic cells is proportional to this rate. One of the major pathways involved in the regulation of apoptosis is the signaling centered around the kinase Akt. We use the in vivo SIV infection of non-human primates as a model of HIV infection together with the model of the in vitro VZV infection of CD4+ T cells to study the association of the rates of activation induced cell death (AICD) with signaling patterns of Akt-GSK3 pathways. These studies show, that differential phosphorylation of Akt at its individual phosphorylation sites plays a role in the response to the virus infection and presence or absence of AICD.This is one of a handful of recent studies indicating the activity of Akt can be specific to only one phosphorylation site and may be linked to the differences in AICD.
University of Jos, Nigeria
Time : 15:35-15:55
Festus Chukwuemeka Onwuliri got his Ph.D. at the age of 35years from the University of Jos. He has previously had his B.Sc., M.Sc. and AIML from the University of Nigeria Nsukka, University of Jos and Medical Laboratory College Vom, Nigeria respectively. He has acquired a wide range of administrative experience. He is currently serving as the Head of Department of Plant Science and Technology, University of Jos and Director of Victory Medical Laboratory Services, Jos Nigeria. Professor F. C. Onwuliri has published about 65 papers in both national and international journals. He has supervised 54 Post Graduate students both at Ph.D. and M.Sc. levels in the area of Microbiology and Biotechnology. He has also supervised over 150 undergraduate students. He has held several other positions and served in several committees, both ad-hoc and statutory, within the University of Jos and other Universities in Nigeria. He has several memberships including memberships in Association of Medical Laboratory Scientists of Nigeria, Nigerian Society for Microbiology, Nigerian Mycological Society, Botanical Society of Nigeria, Nigerian Society for Parasitology, Biotechnology Society of Nigeria, International Biotechnology. Professor Onwuliri participated in the 4th world congress on Biotechnology in North Carolina, USA and registered for 5th world congress on Biotechnology scheduled for 25th to 27th of June this year in Valencia, Spain. He has many Scholastic Honours and Awards. Professor Onwuliri is happily married to Dr (Mrs.) Edith A. Onwuliri and are blessed with 6 Children.
Background: Hepatitis B Virus (HBV) infection is a major health problem and may lead to chronic hepatitis, cirrhosis and Hepatocellular Carcinoma (HCC). Detecting hepatitis B virus variants and antigenic variation of the HBsAg in relation to different geographic areas and process of treatment is fundamental for laboratory assay design, vaccine formulation, and prediction of progression of disease to chronic hepatitis and HCC. Methods: HBV markers were assessed using serum from apparently healthy subjects. HBV markers included hepatitis B surface antigen (HBsAg), hepatitis B surface antibody, and hepatitis B core antibody (HBcAb). Results: Samples from 200 volunteer subjects were tested.17 out of 200 (8.5%) showed evidence of HBV infection. Prevalence of various markers was also assessed among the population of study. Outcome of the Aminotransferase assays conducted showed high level of Transaminase. Conclusion: HBV seroprevalence is high amongst study population. Routine screening for HBV is needed while an urgent public enlightenment is highly encouraged, alongside a regular vaccination schedule.