2nd Global summit on

Virology

November 14-16, 2016, Kuala Lumpur, Malaysia

Scientific Programme(Day 1 : Nov-14-2016)

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Virotherapy

Session Introduction

AE Aboulata
Plant Path. Res. Inst., Egypt
Title: HBV-Molecular Biology Overview and Virotherapy Innovation in the Middle East

Biography: Dr Aboul-Ata Elnady ABOUL-ATA, Professor Dr. of Plantvirology, who was born on Mar.22nd 1948 in Sharkia, Egypt, is the president of ArSV (Arab Society for Virology) in 2013 for 3 years. He was formerly Department Head of Plant Virus and Phytoplasma Research, Plant Pathology Research Institute at Agricultural Research Center, Giza, Egypt for 3 years (2003-2006), and Head of Molecular laboratoryat Plant Virus and Phytoplasma Res. from Sep. 2005 up to now. In 2007 he has been awarded committee membership of Egyptian Society of Advanced Material and NanoTechnology.He is being a committee-member of Egyptian Society of Virology(ESV) since initiation in 2001 up to now. He is the General Secretary for ESV since 2014 for 3-year period. He is beingmember of the Molecular Virology Group at the University of Kentucky, USA, American Phytopathological Society, The New York Academy of Sciences, American Society for Microbiology, Federation of British Plant Pathologists (FBPP) UK, Egyptian Society of Entomology, Egyptian Society of Plant Pathology, Egyptian Society of Applied Microbiology, African Virology Associan (AVA), South Africa, Who'sWho in the World, Record # World-18, 2001 GNNF 2852757104, USA. He is partner as ArSV president and keynote speaker for 3 successive international congress on virology i.e. International Congress on Virology organized by OMICS and ArSV, that will be held in Baltimore, USA during Nov. 20-22, 2013, MENA (Middle East and North Africa) organized by Science International and ArSV that will be held in Dubai during Jan. 21-23, 2014 and STDs organized by OMICS and ArSV that will be held in Sweden during 2014.

Abstract: : HBV-Molecular Biology Overview and Virotherapy Innovation in the Middle East ABSTRACT: Hepatitis B virus (HBV) is one of the world’s major infectious diseases with 350 million people who are chronic carriers of HBV. Significant minorities go on to develop liver cirrhosis or hepatocellular carcinoma and over 1 million die annually from HBV-diseased liver. HBV genotype D is prevalent in our Middle East area. Moreover two genotypes were recently isolated and partially identified. The HBV genome is a partially relaxed-circular dsDNA molecule consisting of a full length strand (minus strand) with a single unique nick and a complementary (positive strand) of variable length. HBV is considered as a para-retrovirus because its replication involves the reverse transcription of an intermediate-RNA function, of pre-genomic RNA (pgRNA). Replication of HBV genome starts with the encapsidation of the pgRNA and encoded HBV polymerase into an immature nucleocapsid formed by the viral core antigen. Inside the immature nucleocapsid, the viral polymerase converts pgRNA into minus-strand DNA, which in turn is used as a template for the synthesis of the plus-strand DNA, resulting in the formation of the characteristic mature double-stranded, relaxed circular DNA molecule. This review briefly describes the molecular biology of Hepatitis B virus, focusing on the structure of the virion and its replication cycle as well as HBV-infection mechanism for HBV diagnostics and control. Control. Proposed CMV-HBVsAg chimeric virus construct could be as follow:CaMV 35s Promoter (35sP), Cucumber mosaic virus (CMV) 26kDa hybrid coat protein (CP D/S) gene for 2 strains (CMV/S and CMV/D) were isolated and amplified from sgRNA 4, 26 kD target gene (HBVsAg) was isolated using specific primers. Replicase gene (RP) and 30 kDa movement protein gene (MP) were used. Nopaline synthase terminator (Nos3T) are constructed between Right and left boarder (RB and LB) to be transfected into tomato as bioreactor host


Antiviral Vaccine Development

Session Introduction

Parvaneh Mehrbod
Pasteur Institute of IRAN, Tehran IRAN
Title: Evaluation of the susceptibility to influenza virus in people suffering from hypercholesterolemia and diabetes in terms of IFITM3 polymorphism rs12252-C

Biography: Parvaneh Mehrbod obtained her Diploma in Natural science in 1994. Parvaneh pursued her tertiary education at Ferdowsi University of Mashhad, Mashhad, IRAN where she received her Bachelor of Plant Biology in 1999. In view of her interest to further her education, she started her postgraduate study in 2006 at Faculty of Science, University of Tehran, Tehran, Iran in the field of Cellular and Molecular Biology and she pursued her PhD study in Molecular Biotechnology at Institute of Bioscience in Universiti Putra Malaysia and graduated in 2013. She was successful to obtain postdoctoral fellowship award from Universiti Putra Malaysia (2014) and currently she is doing another postdoctoral study in Pasteur Institute of IRAN. During her study, she actively involved and participated in national and international conferences, workshops and seminars related to her field. She published some of her research findings in peer reviewed journals and conference proceedings, and has many more under writing and revising.

Abstract: *Influenza Research Lab, Virology Department, Pasteur Institute of IRAN, 13164, Tehran, IRAN Viral respiratory diseases, especially influenza viruses are amongst the most common causes of human diseases. Influenza A virus is one of the most important health risks that lead to significant respiratory infections. Its continuous antigenic changes and resistance to conventional drugs and lack of promising vaccines are the reasons for unsuccessful treatment of influenza. Thus, research to identify new strategies to control the prevalence of influenza disease is necessary and useful. The family clustering of avian influenza cases has led to speculation that host genetics play a critical role in susceptibility to influenza. Several genes have been shown to be involved in host susceptibility and severity to viral infections. Amongst them IFITM and especially IFITM3 has shown the most promising role in resistance to several viruses like West Nile virus, dengue virus, rhinovirus, corona virus, respiratory syncytial virus and influenza A virus. Hypercholestrolemia and diabetes are other critical involved factors in severity of influenza infection which themselves underlie other diseases and previous studies have shown that this virus infection is more severe in these patients. These are concerned in relation to IFITM3 polymorphism rs12252-C in this study. A better understanding of the biological determinants and pathways leading to severe flu may lead to improved therapeutic options. Influenza Research Laboratory in Pasteur Institute of Iran as a health reference laboratory partner in flu prevention and detection policies plays an important role in this way. Therefore, we decided to launch this procedure and then assess the Iranian community’s sensitivity to influenza virus in a national campaign to evaluate the country's needs to vaccine. Keywords: influenza, hypercholesterolemia, diabetes, IFITM3, polymorphism


Rajan George
Alberta Canada
Title: Development of a Dendritic Cell Receptor-Targeted HBV Therapeutic Vaccine

Biography:

Abstract: BACKGROUND: Therapeutic vaccines that induce strong host immune responses are needed to resolve chronic HBV infection. Akshaya’s vaccines/therapeutics are recombinant fusion proteins of antigen(s) and xenotypic antibody Fc fragment. Fc directs the chimeric molecules to receptors on dendritic cells (DCs) and other antigen presenting cells for antigen uptake, processing through both proteasomal and endosomal pathways, and presentation to T cells, which elicits cellular and humoral immune responses against the selected antigens. Akshaya’s HBV therapeutic vaccine incorporates HBV S1 and S2 fragments, core, and a murine Fc fragment. METHODS: The vaccine produced in Sf9 insect cells was purified by affinity chromatography. PBMCs or purified T cells from un-infected or chronically HBV-infected donors were activated ex vivo by co-culturing with vaccine-loaded mature DC (mDC). T-cell proliferation, production of IFN-γ, TNF-α, Granzyme B and Perforin were measured by FACS. HBV-specific CTL response was measured using real-time cell microelectronic sensor (RT-CES) system. Sheep were vaccinated three times at four week intervals with the HBV vaccine, humoral and cellular immune responses were quantified. RESULTS: Stimulation of T cells with vaccine-loaded mDC from un-infected and chronic HBV carriers resulted in T cell proliferation, production of HBV antigen-specific IFN-, TNF-a, Granzyme B and Perforin in CD4+ and CD8+ T cells. In PBMCs from chronically HBV-infected patients, the vaccine induced the production of T responder (CD4+CD25-) cells which are capable of killing T regulatory (CD4+CD25+) cells. Activated T cells from both un-infected and HBV-infected donors killed vaccine/antigen-loaded target cells. In addition, the vaccine generated robust humoral and cell-mediated immune responses in vivo in sheep. CONCLUSION: The vaccine-dependent expansion of IFN-g, TNF-a, Granzyme B and Perforin producing CD8+ and CD4+ T cells, Tresp-induced apoptosis of Tregs in chronically infected donor PBMCs, and CTL-mediated killing of target cells by vaccine-activated HBV infected donor T cells show that the vaccine can break HBV tolerance in chronic HBV carriers. The ex vivo results and the induction of antigen-specific cellular and humoral immune responses in vivo in sheep show the excellent potential Akshaya’s HBV therapeutic vaccine has for the treatment of chronic HBV infections. Financial support from NRC-IRAP Canada is gratefully acknowledged


S. Louise Cosby
Queen’s University Belfast
Title: Measles: Need for continued vaccination and novel vaccines post virus eradication

Biography: Professor S. Louise Cosby (SLC) was appointed as Head of Virology Branch at the Agri-Food and Biosciences institute, UK, in 2015. She was Chair of Microbiology in Queen’s University Belfast from 2002 and remains an emeritus professor. SLC is a Fellow of Royal College of Pathologists (London) and Fellow of the Royal Society of Biology, UK. She has served/currently serves on grant/editorial boards: BBSRC, UK; Chair/member, Science Foundation Ireland; Deputy Chair Professional Development Committee, Microbiology Society, UK; Associate Editor, Journal of Neurovirology, USA; Review editor, Frontiers in Microbiology; External Assessor for Appointments and Promotions in Medical Microbiology, University of Malaysia.

Abstract: Measles virus (MV) is the only human virus within the morbillivirus genus of the Paramyxoviridae. The virus can cause severe complications such as measles giant cell pneumonia and acute post measles encephalitis. More rarely fatal infections of the CNS, subacute sclerosing panencephalitis (SSPE) and in immunosuppressed individuals measles inclusion body encephalitis (MIBE) occur. The World Health Organization (WHO) has set goals towards the complete eradication of MV in at least five WHO regions by 2020. This presents potential problems as the closely related veterinary members in the genus share common cell entry receptors, which we an others have examined, raising the risk of zoonotic infection. MV is thougth to have evolved from the now eradicated cattle morbillivirus, rinderpest, and to have entered the human population during cattle domestication. Lessons have also been learned from other animal to human virus transmission i.e. human immunodeficiency virus (HIV) and more recently avian influenza, severe acute respiratory syndrome (SARS) and Middle Eastern Respiratory Syndrome (MERS). This highlights the potential consequences of complete withdrawal of MV vaccination after eradication. The measles vaccine is live attenuated and has very low risk of reversion but is still unlikey to be acceptible in a MV free world raising the need for alternative approaches. A formalin fixed MV vaccine was used for a period in the 1960’s but provided short lived and non-complete immunity with an altered immune response and death of some children following later infection. This has encouraged research into recombinant vaccines for MV using other virus vector systems which will be discussed.


Valentina A. Divocha
Doctor of Medicine, Professor Odessa, Ukraine.
Title: Study of the protective properties of proteinase inhibitor in experimental influenza

Biography: Divocha Valentina in 1967 she graduated from I. I. Mechnikov Odessa State University, Faculty of Biology (Department of Virology). In 1973 continued her postgraduate study ate Odessa Institute of Virology and Epidemiology (specialty virology). In 1974 she was awarded her candidate degree with the thesis "Interaction of Coxsackie B viruses with sensitive cell cultures and their antigenic relationships." In 2009 she was awarded her doctoral degree with the thesis entitled "Biological basis antiprotease therapy of influenza."Under her leadership performed a doctoral and two master's theses. Scientific experience is 35 years. I have more than 186 scientific publications, 2011 monograph, textbook "Virology" (2012), 10 patents, 3 innovations. I am currently working as the head of the Laboratory of Experimental and Clinical Pathology for Ukrainian Research Institute of Transport Medicine, is the supervisor of the nine research programs in virology and biochemistry.

Abstract: Study of the protective properties of proteinase inhibitor in experimental influenza Divocha Valentina A. State Enterprise Ukrainian research Institute for Medicine of Transport, Odessa, Ukraine. Background. Proteinase inhibitors are widely used in various inflammatory processes. Dedicated us inhibitors we used for the treatment of influenza virus. The objective. Study of the protective properties of proteinase inhibitors in experimental virus influenza. Materials & methods. For the study used: influenza virus A/PR/8/34, 90 white mice of BALB/c line weighting 16-18 g and the 5th isoform of proteinase inhibitor isolated from the wastes of the 1st stage of gamma-globulin production. The mice were divided into 7 groups: 1 - virus control, 2 – virus + trypsin, 3- virus + inhibitor 5th isoform, 4 - 5th isoform, 5, 6, 7 – trypsin control, phosphate buffer, mice control. Both influenza virus, trypsin and inhibitor was administered intranasal under light ether anesthesia during seven days. Each mouse got up to 140 µg of the inhibitor for the course of treatment. The mice were divided into 7 groups containing 15 items in each, with 10 items in control groups. The animals of the first group received lethal dose of virus (virus control). The virus was administered intranasal in a volume of 0.05 ml under Rausch anesthesia. The second group of animals got a similar dose of virus, but they were treated with crystalline trypsin (control of medical properties of crystalline trypsin) in the same doses and terms as the animals of the 3rd group. The third group of animals was infected with the same dose of virus and was treated with trypsin-like proteinase inhibitor of proteinases from the wastes of gamma-globulin production (control inhibitors toxicity). Crystalline trypsin (trypsin control) alone was introduced to the animals of the fifth group, the sixth group got phosphate buffer, with we diluted virus inhibitor and trypsin. The seventh group was used as the control of intact animals. Both trypsin and inhibitor was administered intranasal under light ether anesthesia during seven days. Each mouse got up to 140 mg of the inhibitor for the course of treatment. Results. As the results of the study, the animals of the 1st and 2nd groups were killed at 6-7 days after infection. In the third group of 12 white mice survived (80%). They remained alive and on the 14th day after infection (time of observation). Animals of other groups (4, 5, 6, 7.) remained alive throughout the observation period. Dedicated trypsin-like proteinases inhibitor was not toxic, as white mice of 4th group survived for 14 days after administration of the inhibitor for the treatment of influenza virus. Conclusions. The 5-th isoform with high inhibitor activitiy was used for the study of therapeutically properties and the experimental grippe A at white mice, protected mice from death at 80%.


Tomáš Hanke
The Jenner Institute, University of Oxford, United KingdomandThe Center for AIDS Research, Kumamoto University, Japan.
Title: Development of an effective HIV-1 T-cell vaccine through targeting conserved regions of the HIV-1 proteome

Biography: Professor Tomas Hanke's research aims to develop a universal HIV-1 vaccine, which targets most global virus variants including escape mutants. He strives to maintain a balance between basic and translational research. He oversees a busy pre-clinical programme encompassing HIV-1 epitope discovery and dynamics using mass spectrometry and T-cell assays, studies on immunodominance, depth (number of variants) of epitope recognition and the importance of perfect vaccine-virus epitope matching for effective effector functions. He explores novel vaccine modalities and optimize their immunogenicity in heterelogous prime-boost regimens in mice and macaques. He co-ordinates a clinical programme assessing candidate HIV vaccines in humans in UK, Europe and Africa.

Abstract: An effective HIV-1 vaccine is the best solution for halting the AIDS epidemic. To deal with HIV-1 diversity, we target the highly functionally conserved regions of HIV-1 proteins. I shallbriefly overview trials with the 1st generation alternating clade consensus HIVconsv vaccines, and describe the design and preclinical immunogenicity of the 2nd generation tHIVconsvX vaccines designed as bivalent conserved-region mosaic. The tHIVconsvXimmunogens combine the three leading strategies for elicitation of effective CD8+ T cells: use of regions of HIV-1 proteins conserved across all M group viruses, inclusion of bivalent complementary mosaic immunogens to enhance epitope matching and immunogenicity, and inclusion of epitopes known to be associated with low virus load in infected treatment-naivesubjects. tHIVconsvXwas highly immunogenic in two strains of mice. Furthermore, the magnitude and breadth of CD8+ T-cell responses to peptides within tHIVconsvX in 120 treatment-naive HIV-1+ patients significantly correlated with high CD4+ T-cell count andlow viral load. These data strongly encourageclinical development of the 2nd generation vaccines for prophylaxis as a complement to Env vaccines and towards HIV cure.


Mazhar I. Khan
Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT 06269-3125, USA.
Title: Vaccination with Novel Protein Nanoparticles Provides Protection against Lethal Influenza Challenge

Biography: Prof. Dr. Mazhar I. Khan’sresearch involved molecular epidemiology and pathogenesis of influenza virus infection. Currently, in his laboratory in developing and testing nanoparticle based avian influenza (bird flu) and infectious bronchitis virus vaccines. He was involved in the development of innovative bioinformatics tool for viral quasispecies reconstruction using next generation sequencing data for the development of optimized viral vaccines. He has long-term experience in development and application of DNA probe, PCR, multiplex PCR, real-time PCR and loop-mediated isothermal amplification (LAMP) methods for rapid detection of viral pathogens in clinical samples. Have made significant contributions in the diagnostic field using DNA techniques in identification of several pathogens of avian, animal and human diseases since 1985. Have mentor visiting international scientists form Asia, Europe and South America.He has an extensive knowledge on pathogenicity studies in embryos infected with infectious bronchitis virus, a coronavirus, which causes stunting and embryo deformity before hatching. As a virologist have extensive knowledge and research involved in the development of diagnostic tests and vaccines for the control of avian viral diseases.

Abstract: Subunit vaccines are generally less immunogenic than whole organism vaccines. One approach to reduce this deficiency is the development of repetitive antigen displays. One of the most promising repetitive antigen displays is our Self-Assembling Protein Nanoparticle (SAPN). Based off of coiled-coil oligomerization domains our SAPNs can self-assemble into spherical particles that mimic the size and shape of small viruses and are decorated on their surface with antigens. We have applied the SAPN technology to the development of a universal Influenza Virus vaccine. By incorporating two conserved antigens (M2e and Helix C) we aimed to generate a vaccine candidate that is broadly protective not only through different seasons, but also against different subtypes. One of the most important considerations in vaccine development is adjuvant formulation. We have designed and implemented a new technology that incorporates the TLR5 agonist flagellin into the SAPN. Flagellin is an established adjuvant that is known to induce increased antigen processing as well as increased humoral and cellular immune responses. By adding flagellin to our SAPNs we have generated Self-Adjuvanted SAPNs. We have applied this technology to the development of universal influenza vaccine. In this study we demonstrate that addition of flagellin does not affect the ability of SAPNs to self-assemble, nor does it change the size or shape of the SAPNs. Self-Adjuvanted SAPNs are able to stimulate TLR5 in vitro in a dose dependent manner. Specific Pathogen-Free Chickens vaccinated with the Self-Adjuvanted-SAPN induce significantly higher levels of antibodies than unadjuvanted-SAPNs. Antibodies from chickens vaccinated with the Self-Adjuvanted-SAPNs are cross-neutralizing towards group1 influenza strains in in vitro experiments. Upon immunization with Self-Adjuvanted-SAPN mice were completely protected against a lethal challenge with A/human/Puerto Rico/8/1934 (H1N1). Our data indicate that we have generated a Self-Adjuvanted-SAPN that has a great potential as a universal influenza vaccine


Viral Hepatitis- Virus-host interactions

Session Introduction

Aleem Siddiqui
Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Title: Human hepatitis virusesdisruptmitochondrial dynamics and attenuate innate immunity

Biography: Aleem Siddiqui is a Professor at the University of California, San Diego. He received his undergraduate and graduate education from Osmania University, Hyderabad, India and Ph.D., degree from the University of Kansas Medical Center, Kansas City, KS. He was a postdoctoral fellow at the University of Colorado Medical School, Denver, CO with Dr. Ray Erikson followed by a second postdoctoral fellowship with Dr. William S Robinson at Stanford University, CA. He was instrumental in the first molecular cloning of an infectious Hepatitis B virus (HBV) DNA at Stanford University in the laboratory of Dr. Stan Cohen in 1979. He then joined the University of Colorado Medical School as an Assistant Professor. His current research focuses on molecular mechanisms of liver disease pathogenesis associated with HBV and HCV viral infections. More recent work is related to lipid and mitochondrial metabolisms and innate immunity during HBV/HCV infections.

Abstract: Track : Viral Hepatitis- Virus-host interactions Human hepatitis virusesdisruptmitochondrial dynamics and attenuate innate immunity Mitochondrial liver injury has been long recognized as one of the serious consequences of hepatitis B and C viral (HBV/HCV) infections.Mitochondrial dynamics involving fusion, fission, and mitophagy is necessary for the maintenance of mitochondrial and cellular homeostasis. However, its abnormality may play a role in the pathogenesis. Here we demonstrate that HBV/HCV shift the balance of mitochondrial dynamics toward fission and mitophagy to attenuate the virus-induced apoptosis, which enables them to establish chronic hepatitis. The mitochondrial translocation of phosphorylated dynamin-related GTPase Drp1 (Ser616) mediates mitochondrial fission. HBV induced perinuclear clustering of mitochondria and promoted Drp1 phosphorylation at Ser616 residue and its mitochondrial translocation followed by mitochondrial fission. HBV/HCV induced Parkin recruitment to the mitochondria followed by mitophagy. Upon translocation to mitochondria, E3 ubiquitin ligase Parkin was self-ubiquitinated and facilitated the ubiquitination and degradation of its substrates. Perturbing mitophagy by silencing Parkin led to enhanced apoptotic signaling, as evidenced by a notable increase in leakage of cytochrome c from the mitochondria, and activation of caspase-3/7 activity, cleavage of caspase-3 and poly (ADP-ribose) polymerase and apoptotic cell death suggesting that HBV-induced mitochondrial fission and mitophagy promoted cell survival.We also observed that mitochondrially recruited Parkin ubiquitinates mitochondrial antiviral signaling protein (MAVS). MAVS serves as the platform of innate immune signaling leading to interferon (IFN) synthesis. In Parkin-silenced cells, IFN synthesis was enhanced substantially, thus hinting that both HBV/HCV attenuate innate immunity via Parkin. Collectively, our results indicate that altered mitochondrial dynamics associated with HBV/HCV infections attenuate cell death and likely contributes to chronic hepatitis. Our studies also highlight the role of mitochondrial dynamics in attenuating innate immunity.


Dr Mohammad Kazemi Arababadi
Rafsanjan University of Medical Sciences, Rafsanjan, Iran
Title: Pathogen recognition receptor pathways are disrupted in the chronic hepatitis B

Biography: Dr Mohamad Kazemi Arababadi has completed his PhD at the age of 30 years from Tarbiat Modares University, Tehran, Iran. He is the director of Immunology of Infectious Diseases Research Center, a research center of Rafsanjan University of Medical Sciences. He has published more than 95 papers in reputed journals and has been serving as an editorial board member of several journals

Abstract: Introduction: Pathogen recognition receptors (PRRs) play key roles in innate immunity against viral infections. It has been also demonstrated that the patients with chronic hepatitis B (CHB) are unable to eradicate HBV from hepatocytes. It has been hypothesized that innate immunity dysfunction may be considered as a main candidate for specific disrupted immune responses against HBV in the CHB patients. Accordingly, our research team have been evaluated the expression levels of TLRs, TLRs signaling molecules (MYD88, TRIF, IRAK1, TRAF6, IRAK4, TRAF3, NF-B and IRF7), inflammasomes (NLRP1, NLRP3, NLRC4 and AIM2), inflammasomes downstream molecules (ASC and Caspase-1), MDA5 and RIG-1 in CHB patients. Material and methods: This study was performed on 60 CHB patients and 60 healthy controls and the expression levels of the molecules were evaluated by Real-Time PCR technique. Results: The results demonstrated that expression levels of TLR9 and its intracellular signaling molecules, MDA5, ASC, Caspase-1 and NLRP3 were significantly decreased in PBMCs of CHB patients in comparison to healthy controls. Conclusion: Based on the results presented here it seems that CHB patients do not express appropriate levels of PRRs in several pathways which may lead to impaired immune responses against HBV infection which is seen in the patients.


Therapeutic Approaches and Targets for Viral Infections

Session Introduction

SURAKSHA AGRAWAL
Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow
Title: Correlation of killer immunoglobulin like receptor genes with the rate of cytomegalovirus infection in renal transplantation

Biography: Suraksha Agarwal was holding the post of Chairperson of the Department of Medical Genetics for 18 years. During this tenure he was looking after the transplant immunology and medical genetics in particular. He looked after the laboratory budget and research grants and full time supervision of the lab and part time supervision of other projects within SGPGIMS, K. G. Medical College and CDRI. he was also responsible for providing diagnostic advice to clinical colleagues and providing focus for training of medical and scientific staff in HLA techniques. He am the recognised PI for DBT sponsored projects and for running the course in post MD/MS biotechnology programme .He actively involved in the formulation of 03 courses, training of post MD/MS biotechnology, teaching DM medical genetics and Ph. D. The courses taken by me for these students are immunogenetics, population genetics, molecular genetics and cancer genetics. So far almost 33 Ph. D’s and 40 DM students have completed their degrees with me. I am also actively participitating in the teaching programme related to M. Phill in translational biology at CSSMU previously known as KGMU. He was in charge of exam cell and chairman of the purchase committee for two years. He have been a active member of the governing body, academic board, chairperson of housing committee from time to time during my tenure in this institute. He was superannuated on 2010 after completing 62 years of my age. Presently he is supervising the HLA laboratory.

Abstract: Abstract Aim: Immune mechanisms of cytomegalovirus (CMV) infection suggest a possible relationship between CMV with development of acute graft rejection. Current immune suppression impairs antiviral specific T-cell immunity in solid organ transplantation. Inhibitory/activating NK receptor bindings activated by self HLA antigens confront allogeneic cells that lack a ligand for specific receptor. KIR ligand incompatibility caused due to presence/absence of KIR receptor in recipient and corresponding HLA ligand by the allograft which is recognized by KIR, may have potential impact on chance of CMV infection and graft survival in renal transplantation recipient. We hypothesized that predominance of matched activating KIR genes and their HLA ligands may downplay the rate of CMV infection among kidney transplant recipients. Methods: We have evaluated matches/mismatches between KIR genes and known HLA ligands among CMV disease (n=27) and primary CMV infected (n=259) conditions among North Indian renal transplant cases. Sequence specific primed polymerase chain reaction method was used for KIR genotyping. Results: Survival analysis revealed increased risk of CMV for individuals carrying inhibitory KIR genes 2DL1 (OR=3.45, p-value=0.013) and 3DL1(OR=3.23, p-value=0.032). While protective association was revealed activating KIR2DS1 (OR=0.32, p-value=0.005). Compatible KIR2DL2-HLA-C1 combination showed protective association (OR=0.23, p=0.031) with its ligand HLA-Bw4. KIR-HLA ligand match-mismatch also revealed protective association (OR=0.95, p-value=0.014) in the absence of KIR3DS1-HLA-Bw4 combination. Conclusion: Graft outcome after renal transplantation revealed prolonged survival in the presence of certain KIR/HLA class I ligand combinations among CMV diseased and primary CMV infected cases. Key-Words Human leukocyte antigen-B, C (HLA-B, C); Killer immunoglobulin-like receptor (KIR); Cytomegalovirus


Alan C Jackson
University of Manitoba, Winnipeg, MB, Canada
Title: Rabies encephalitis: advances in our understanding of the disease and new therapeutic approaches for the future

Biography: Dr. Jackson is Professor of Medicine (Neurology) and of Medical Microbiology and also Head of the Section of Neurology at University of Manitoba in Winnipeg, Manitoba, Canada. He graduated from medical school at Queen’s University and completed an internship at University of Southern California, residencies in internal medicine at Queen’s University and in neurology at the University of Western University, and a fellowship in neurovirology at Johns Hopkins University with the late Richard Johnson and with Diane Griffin. Dr. Jackson was the first President of Rabies in the Americas, Inc. and he has served on the Board of Directors of the International Society for Neurovirology. He is a fellow of the Royal College of Physicians and Surgeons of Canada, the American Neurological Association, and the American Academy of Neurology and a member of the American Society for Virology. Dr. Jackson has done research on the pathogenesis of rabies and edited/coedited four books on rabies and one on viral infections of the nervous system.

Abstract: Rabies is an acute viral infection of the nervous system caused by rabies virus. The infection is usually transmitted by an animal bite. Worldwide, about 60,000 humans die of rabies every year and many are children. Most deaths are related to the presence of endemic canine rabies and dog bites. Canine rabies is now well controlled in Latin America using mass vaccination of dogs, but remains uncontrolled in Asia and Africa. Rabies can very effectively be prevented after recognized exposures, but is virtually always fatal after the development of the disease. To date there have been no real advances in the therapy of human rabies. The Milwaukee protocol (therapeutic coma, ketamine, ribavirin, and amantadine) was strongly promoted, but lacked a sound scientific rationale and proved to be a failure. The difficulty in developing new therapeutic approaches is, at least In part, related to a lack of understanding of basic mechanisms underlying the disease. There is recent evidence of neuronal process degeneration, affecting axons and dendrites, in experimental rabies in mice. Studies in cultured adult rodent primary dorsal root ganglion neurons show evidence of oxidative stress with axonal swellings and reduced axonal growth and there is evidence of mitochondrial dysfunction. The rabies virus phosphoprotein interacts with mitochondrial Complex I, increasing its activity and resulting in the overproduction of reactive oxygen species, which play an important role in neuronal injury. This improved understanding of rabies pathogenesis may lead to important advances in developing novel therapies for this ancient disease.


Girish J. Kotwal
UMass Medical School, Worcester, MA, USA, Kotwal Bioconsulting, LLC, Louisville, KY, USA
Title: Broad spectrum antivirals: nature's magic bullets against currently pandemic virus infections like HIV and emerging viral infections like Zika, Ebola and bird flu

Biography: Girish J. Kotwal, Ph.D. has worked on a number of clinically important viruses like HIV, HCV, pox viruses, herpes viruses, etc at a number of institutions in Canada, USA and South Africa and has over 100 pubmed listed publications and over a dozen patents. He was a Visiting fellow and later a visiting associate at the National Institute of Health , Bethesda, MD, USA, a tenured Associate Professor at University of Louisville School of Medicine, Professor and Chair of Medical Virology at the University of Cape Town and is currently Adjunct Professor of Medicine at UMass Medical School.

Abstract: Background/Introduction Pandemic viral infections like HIV can be treated effectively with multiple antitrovirals but there are 3 problems with this line of treatment. The cost and availability is prohibitive for some patients. The antiretrovirals can give rise to a number of adverse effects and the current guidelines for treatment which requires the CD4 counts to come down to either 350 or less can make early intervention difficult. There is no preparedness for new pandemic strains of Influenza and emerging viral infections as was experienced with recent Ebola outbreaks in western Africa or the expanding spread of Zika virus. Our group of collaborators has been interested in addressing these issues of public health and has been evaluating the possibilities of deploying natural broad spectrum antivirals to combat pandemic virus infections as well as emerging new strains and viruses. Aims/Objectives To determine and evaluate possible compounds that are naturally present and to test theis viricidal effects on a wide range of enveloped viruses. Most of the research has centered around pomegranate juice and fulvic acid but other natural products have also been tested, Method The first step in evaluating a natural substance is to test for cell toxicity at concentration which will be used for testing antiviral activity. The second step is to treat about a million virus particles of vaccinia virus with about 50 micoliters of sterile antiviral preparation and determine whether the level of infectious virus particles is very significantly reduced. Results Our results have shown that 100% sterile pomegranate juice is able to neutralize a million vaccinia virus particles within 5 minutes. Fulvic acid was able to do the same in 1 minutes at concentrations at which neither of them are toxic to the cells. Neutralization of a multiple Influenza strains was also found to occur with the treatment with either POM or Fulvic acid. The same was repeated with SARS and Herpes viruses. Discussion/Conclusion Our research with natural broad spectrum antivirals demonstrate the potential of these safe compounds in inactivating pandemic viruses and enveloped emerging viruses. Pomegranates are available almost everywhere on our planet and could form the first line of attack against emerging viruses against which no vaccines exist or no treatments are available.


Volker Patzel1
Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore
Title: Selective killing of virus-transduced or cancer cells using a RNA trans-splicing based suicide gene therapy approach

Biography: Dr. Volker Patzel, chemist, received his Ph.D. from the RuprechtKarls University in Heidelberg and his MBA from the Steinbeis University in Berlin. He worked as postdoc at the German Cancer Research Centre in Heidelberg and then as research group leader at the Max Planck Institute for Infection Biology in Berlin. Currently he holds a dual appointment as Assistant Professor at the National University of Singapore and Assistant Director of Research at the University of Cambridge. He is founder and director of the Steinbeis Transfer Centre for Nucleic Acids Design. His research focuses on the design and delivery of ribonucleic acids for enhancement, inhibition or repair of gene expression towards diagnostic and therapeutic applications.

Abstract: In mammalian cells, spliceosome-mediated RNA trans-splicing may occur accidentally or be a mechanism used by distinct viruses to support the diversification of viral RNA and proteins.First we studied the highly efficient mechanism of trans-splicing among transcripts of the simian virus 40 (SV40).Then we employed molecular features of SV40 RNA trans-splicing and computational RNA structure design to improve both on-target activity and specificity of trans-splicing RNA (tsRNA) in a Herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) suicide gene therapy approach. As molecular targets we selected the-fetoprotein (AFP),a marker of hepatocellular carcinoma (HCC), human papillomavirus type 16 (HPV-16), or human immunodeficiency virus type 1 (HIV-1) pre-mRNA. While unstructured mismatched target binding domains significantly improved 3’ exon replacement, 5’ exonreplacement correlated with the thermodynamic stability of the tsRNA 3’ end. Alternative on-target trans-splicing was found to be a prevalent event. The specificity of trans-splicing with the intended target splice site was improved 10-fold by designing tsRNA harbouring multiple target binding domains shielding alternative on-target and blinding non-target splicing events. Rationally designedtsRNAs efficiently and selectively triggered death of HPV-16, HIV-1 or AFP-positive cells. Dual-targeting tsRNA simultaneously targeting AFP and a second HCC biomarker triggered enhanced cell death at 10-fold lower GCV doses. Our observations suggest RNA trans-splicing represents a promising approach to suicide gene therapy.


Agriculture and Plant Virology

Session Introduction

Nagwa M. Amin Aref
Saudi Arabiaâ
Title: Method of Inhibiting Plant Virus Using Gold Nanoparticles

Biography: Nagwa Mohamed Aref is a Molecular Virologist graduated from Microbiology Department Ain Shams University in 1974, Cairo, Egypt. She obtained her .Ph.D. in Plant Virology as channel system study with University of Hohenheim, Institute fur phytomidizine, Stuttgart, Germany in 1984. She worked as a staff member in Microbiology Department until 2000.Participating in the detection of Plant viral disease of the research program 1984-1989 at Michigan State University East Lansing, USA. Co-investigator at AGERI (Agriculture Genetic Engineering Research Institute), Ministry of Agriculture, Egypt, 1990-1996 in UNDP project entitled:” Engineering transgenic tomato plants resistant for Tomato Yellow Mosaic Gemini Virus” in contribution to Scripps Research Institute, San Diego, USA. Exchange Visitor professor for a short term research scholarship in Electron Imaging Center, California NanoSystem Institute (CNSI).The University of California UCLA, Los Anglos USA in 2008. She published more than 40 publications; she is working now as a professor in College of Science, King Saud University, Department of Botany and Microbiology in Saudi Arabia. Recently, she focused on the studying application of using nanoparticles and its effects on plant virus particles to induce resistance to the plant virus and having a PATENT. Study and diagnose the diversity of Virus Strains in a different ecosystem.Interested in the immune response and prognostic serological markers for HBV and HCV in Saudi cohorts.

Abstract: ABSTRACT The method of inhibiting a plant virus using gold nanoparticles is a method of inducing plant resistance against viral disease caused by Barley Yellow Mosaic Virus (BYMV) particles by introducing a therapeutically effective amount of polydispersed gold nanoparticles to the plant through a mechanical abrasive, wherein the average effective diameter of the nanoparticles is between about 0.5 nm and 200 nm and wherein the gold Nanoparticles are present at a concentration of about 1.0.times.10.sup.-5 G/ml to about 6.times.10.sup.-4 g/ml, and wherein the gold nanoparticles melt and dissolve the virus particles.


Kathleen Laura Hefferon
Cornell University, New York
Title: Plant Expression Platforms for Vaccine Production

Biography: Kathleen Hefferon received her PhD from the Department of Medical Biophysics, University of Toronto and continued her post-doctoral studies at Cornell University. Dr. Hefferon has worked on faculty at the Division of Nutritional Sciences at Cornell and has written two books on biopharmaceuticals in plants. She teaches and conducts research at both the University of Toronto and Cornell University. Kathleen has 4 patents, has edited 6 books, and has multiple research publications. Kathleen currently lives with her family near Ithaca NY.

Abstract: Abstract Plant made biologics have elicited much attention over recent years for their potential in assisting those in developing countries who have poor access to modern medicine. Additional applications such as the stockpiling of vaccines against pandemic infectious diseases or potential biological warfare agents are also under investigation. Plant virus expression vectors represent a technology that enables high levels of pharmaceutical proteins to be produced in a very short period of time. Recent advances in research and development have brought about the generation of superior virus expression systems which can be readily delivered to the host plant in a manner that is both efficient and cost effective. The following presentation describes recent innovations in plant virus expression systems and their uses for producing biologics from plants.