Clinical studies and field trials
Biography: Akram Najafi is from The Persian Gulf Marine Biotechnology Research Center, Bushehr University of Medical Sciences, Bushehr, Iran.
Abstract: Background: Rotaviruses are one of the most important causes of acute gastroenteritis in children under 5 years old. With the licensure of new RV vaccines, data on the burden of disease are important regarding immunization strategies.
Objectives: The aim of this study were to monitor the disease burden associated with rotavirus and determine the G genotypes of rotavirus circulating in Shiraz, Marvdasht, Jahrom and Borazjan, South of Iran.
Methods: Overall, 788 fecal samples were collected from less than 5 years children with diarrhaea admitted to hospitals in cities mentioned above. All the stool specimens were tested for rotavirus with EIA. Rotavirus-positive specimens were genotyped by Nested RT-PCR method.
Results: Out of the total collected samples, in 34.78%, 28.37%, 46.01% and 25.43% rotavirus infection was detected in Shiraz, Marvdasht, Jahrom and Borazjan respectively. Overall, in the common genotypes, non-typeable was the most predominant (31.47% of strains). The frequency of G1, Mix, G4, G2, G9, and G3 were 25.50%, 16.73%, 16.73%, 6.37%, 2.39% and 0.8% respectively.
Discussion: Because of the high frequency of rotavirus infection is important to continue rotavirus surveillance in the other Iran regions to determine accurately the burden of rotavirus disease and the emerging new genotypes. This will assist policy makers in decision making on rotavirus vaccine introduction and determining the impact of the vaccine.
Conclusions: The Noticeable frequency of non-typeable genotypes indicate that must be using from another primers and also detection of unusual genotypes by other specific primers.
Keywords: Rotavirus, Genotyping, Nested RT-PCR, Acute Gastroenteritis
Biography: Prof Patrone Rebecca Risenga has expertise in HIV and HIV counselling and Testing services.. She has developed an educational programme to encourage young adults to go and test for HIV using Dickoff six survey list; namely, agent, recipient, context, procedure, dynamic and terminus, . She has many publications which are viewed by different scholars.
Abstract: The World Health Organization estimates that 80% of the worldâ€™s population complements conventional therapy with traditional folk medicinal therapies in some aspect of their health care and the most popular of these are herbal therapies (WHO 2008) In Africa, a wide range of traditional herbal medicines are used as part of therapy by the majority of HIV positive people (Ozsoy & Ernst 1999). Moringa leaf contains all amino acids (including the essential ones) vitamin A B C D complex, K, macro and micro mineral elements including selenium and zinc among others and this is one of the herbs used by patients who are HIV positive.
Purpose of this study is to describe the perceptions of patients on Moringa regarding their health. A cross-sectional, explorative, descriptive research design was applied. The sampling frame was all HIV-infected adults presenting to the clinic with opportunistic infection in one of the clinics in Capricorn district Limpopo Province. Participants had to be already enrolled in the national antiretroviral program. Participants were selected as a convenience sample of patients who came to the clinic during July to October 2014 on one afternoon a week.
ï¶ Data analysis was done by categorizing, ordering, and summarizing the data, and describing the findings.
- Moringa was seen as a best booster amongst patients who are HIV positive in relation to opportunistic infections
- Effect of Moringa in CD4 cell count
- Moringa and drug interactions
Moringa was seen as a herb with a huge impact on HIV and many patients are using it on daily basis Key words: Moringa, HIV positive
Biography: Festus M. Tolo, Ph.D., is a Medical Microbiologist holding a Doctor of Philosophy Degree in Medicinal Phytochemistryof Jomo Kenyatta University of Agriculture and Technology (JKUAT). Principal Research Officer at the Centre for Traditional Medicine and drug Research (CTMDR) and Head, Natural Products Research and Drug Development Programme (NAPREDA), KEMRI. A fellow at the African Scientific Institute (ASI) and a WHO Special Program for Research and Training in Tropical Diseases (TDR) trainer in Good Laboratory Practice (GLP). My engagements in medicinal plants research spans over two decades where I have been involved in various research projects, notably, the JICA sponsored Infectious Diseases Research Programme of KEMRI where I played a key role in the “Plant Drug Research Group for Antiviral Agents” leading to the patenting of an anti-herpes drug, Zedupex. I have been a project manager of a WHO/TDR funded project on the “Investigation of Safety, Efficacy and Chemistry of Herbal Medicines used Traditionally for Treatment of Malaria” and was a lead scientist in the National Council for Science Technology and Innovation (NACOSTI) funded project on the “Natural Products Innovation System: Establishing a National Nutraceuticals and Phytomedicines Development Pipeline”. I am presently a Principal Investigator (P.I.) of two projects funded by the Government of Kenya (GoK), one evaluating local medicinal plants in Kenya with potential anti-asthmatic activity and another on new biomedical uses of Chrysanthemum cinerariaefolium(pyrethrum) locally grown in Kenya.
I am a part time lecturer in Medical Microbiology at JKUAT Karen campus and presently supervising 12 undergraduates, 4 MSc and 3 Ph.D. students. I am a peer reviewer for the Commission of University Education (CUE), Kenya.Due to my continuous efforts in search for herbal remedies for management human infections, I was awarded the KEMRI Gold prize for outstanding research (The Nelion Gold Award) by the KEMRI board of management in December, 2014 and a commemorative trophy by the China Academy of Chinese Medical Sciences (CACMS) in Beijing, China, in September, 2015.
Abstract: TMR5 is a product of a Kenyan medicinal plant, prepared as a lyophilized extract and a cream. The products have been evaluated for preclinical safety and efficacy in suitable in vitro and in vivo
systems of herpes infections. Herpes is a viral infection affecting over 60% of the sub-Saharan Africa
young adult population. It is caused by two similar viruses, HSV-1 and HSV-2 which share 50% gene
sequence homology. The infection in a major cause of genital ulcer disease, associated with increased
risks of HIV acquisition and transmission in the region.
To develop TMR5 as an alternative therapeutic agent for herpes infection management.
The plaque inhibition and viral yield reduction assays were applied in vitro for assessment of antiviral
activity. Toxicity was evaluated by the trypan blue exclusion method. In vivo, Mice and guinea pig
cutaneous and genital HSV infection models were used respectively to evaluate efficacy following
oral and topical treatments.
Cytotoxic concentrations of TMR5 in mammalian cell lines indicated a wide therapeutic index (CC50
≥58.5±4.6μg/ml). An EC50 of ≤14.73.7μg/ml for both wild type and resistant strains of HSV was
realized in plaque and viral yield assays. Oral (250 mg/kg) and topical (10% cream) administrations
exhibited a significant delay in onset of infections, hindered progression of infection to lethal forms
with increased mean survival times and low mortality. No acute toxicity has been realized at the
TMR5 has demonstrated potential as an anti-herpes agent and arrangements are presently underway to
evaluate its efficacy and safety in a higher mammalian model.
Biography: Yvonne Ajamma, an entomologist, a virologist and geneticist, recently completed her doctoral research in the population ecology and genetic diversity of arbovirus mosquito vectors in the islands and mainland shores of two lakes in Kenya at the International Centre of Insect Physiology and Ecology (ICIPE), Kenya. She got her B.Sc. in Parasitology and Entomology (PAE) from Nnamdi Azikiwe University Awka in Nigeria in 2008, and M.Phil. in Entomology from University of Ghana in Ghana. After her first degree, she received the prestigious fully funded German Academic Exchange Service (DAAD) scholarship to do her masters in Ghana on the surveillance and molecular identification of the urban, peri-urban and rural Aedes mosquitoes that are likely arthropod borne virus (arbovirus) vectors. She performed the Sanger-sequencing of the Aedes samples she collected. She graduated as the best M.Phil. student of her set, which gave her an edge to obtain another fully funded Swedish International Development Cooperation Agency (SIDA) scholarship for her doctoral studies and research. Dr. Ajamma has co-authored five peer-reviewed scientific publications. She was the PhD Students’ Representative and President of all ICIPE graduate students during her PhD research in ICIPE. She received the 2014 one year membership award for mosquito essay from Pan African Mosquito Control Association (PAMCA). She is a member of African Society for Bioinformatics and Computational Biology (ASBCB) and African Association of Insect Scientists (AAIS).
Abstract: Many mosquito borne viruses have been implicated in viral related illnesses of both humans and animals in Kenya. Although epidemics of vector-transmitted emerging infectious diseases have risen in frequency in recent years, the extent to which the mosquitoes contribute to maintaining pathogens in circulation during inter-epidemic periods has received little attention. This study investigated the occurrence of transovarial maintenance of arthropod borne viruses (arboviruses) in different mosquito species in and around Lake Baringo and Lake Victoria in Kenya. Mosquito larvae were collected using standard dippers, reared to adults and identified. Mosquito pools comprising ~25 individuals per species were screened for the presence of mosquito borne viruses by culture and PCR-high resolution melting techniques. Pools of Culex univittatus and Anopheles gambiae were positive for Bunyamwera virus, a pathogenic virus that is of great public health concern. In addition, 11 pools of Aedes, Culex and Anopheles species were positive for insect-specific flaviviruses, namely Culex flavivirus, Aedes flavivirus and Anopheles gambiae flavivirus respectively, that are non-pathogenic to humans and animals. Interestingly, these mosquito specific viruses were, also, found in the same vectors of pathogenic viruses. These data show that some pathogenic viruses are maintained in circulation even in the absence of vertebrate hosts. Better surveillance of mosquito vectors even in the absence of epidemics could be used to forecast changes in vector-pathogen dynamics and disease risk, hence informing prevention and vector management strategies.
Biography: Madhukhanna is from Vallabhbhai Patel Chest institute, University of Delhi, Delhi, India
Abstract: Chikungunya virus (CHIKV) infection lead to the induction of various signaling cascades closely linked to the pathogenesis or propagation of virus. Unfolded protein response (UPR) and autophagy are among the major processes maintaining the cellular homeostasis.These pathways protect the cell in several ways during viral infection, but some viruses developed strategies to either block these processes or exploit them for their own replication. Viral infection overload the ER lumen by production of viral encoded protein, which may leads to the activation of UPR response while autophagy is generally constative as basal level, up-regulate in response to cellular stress or pathogen infection. Autophagic responsedegrade misfolded or aggregated proteins, clear damaged cellular organelles, even eliminate intracellular pathogen. Disruption of either of these process severely affect cellular homeostasis. We have studied the activation of UPR and autophagy pathway during chikungunya virus infection and also the crosstalk between these processes.in-vitro induction of ER stress in chikungunya infection is evident by the nuclear translocation of ATF-6 which was validated by western blotting and confocal microscopy. Activation of IRE1/XBP1 pathway was also confirmed by real time PCR. We alsoobserved crosstalk between UPR activation and autophagy,as silencing of key UPR pathways using siRNA also affectautophagy. Viral replication was inhibited by silencing of autophagy. Hence, the autophagy favor viral replication, and could be exploited for designing antivirals against chikungunya along with UPR pathway.
Biography: Jacques Choucair is from Department of Infectious Diseases,, Hôtel-Dieu de France, Beirut, Lebanon
Abstract: Objectives: To evaluate the knowledge of urban adult Lebanese women regardingthe symptoms and risk factors of cervical cancer and the diagnostic tests and vaccination of human papillomavirus (HPV) infection. To measure in the same population the uptake of the cervical cancer-screening test (Pap smear) and the uptake of HPV vaccination, and determine the factors that may influence them.
Methods: 444 Lebanese women above 18 years of age, residing in Beirut and Mount-Lebanon, with no medical background, were recruited online and in health care facilities to fill out a 32 item questionnaire about cervical cancer and HPV. Collected data was exported to and analyzed in SPSS® v. 21.0.
Results: 45.7% of the women aged 18 to 25 y, residing in Mount-Lebanon (51.8%), single (49.3%), with high education qualifications (73.9%) and currently employed (49.1%) in a field not related to health (84.9%). They did not visit a general physician (64%) or a gynecologist (64.6%) regularly. 85.6% were aware of cervical cancer; HPV infection involvement in the pathogenesis of cervical cancer was identified in 53.9% of cases. 35.6% of women were aware of HPV infection but 80.4% believedthey lack information. 37.6% of participants had been screened by Pap smear for cervical cancer at least once whereas 9% did not know what a Pap smear was. Screening was significantly associated with cervical cancer awareness and regular visits to general health physicians and gynecologists. Only 11.7% of participants aged 18 to 35 were vaccinated against HPV. Vaccination uptake was significantly associated with cervical cancer awareness, religion, field of work and studies, and regular visits to gynecologists.
Conclusion: urban Lebanese women in Beirut and Mount-Lebanon are not well informed about cervical cancer and HPV. Screening by Pap smear and HPV vaccination uptakes are non-satisfactory. Further interventions are required to improve these numbers.
Biography: Oladele Damilola Modupe is from Department of Paediatrics, University of Ilorin Teaching Hospital, Kwara State, Nigeria
Abstract: Globally, RSV contributes a significant aetiologic burden to under-fives ALRI. RSV ALRI however occur with or without concomitant bacteraemia. The need to differentiate RSV ALRIwithout bacteraemia(where treatment is essentially supportive) from those with bacteraemia (where antibiotics are indicated) is thus paramount, to foster antibiotic stewardship. In-spite of this obvious need, routine identification of RSV infection is impeded by the prohibitive cost of viral detection in most tropical settings. This study was thus conceived against this background, to identify clinical predictors of RSV infection with a view to differentiating RSV infection with bacteraemia from those without bacteraemia.
The study was a descriptive cross-sectional study where 120 hospitalized children with severe ALRI (bronchiolitis and pneumonia) were consecutively recruited over a 12-month period. Relevant clinical features, chest radiographs as well as nasal washings for RSV detection using chromatographic immunoassay and blood for blood culture were obtained at presentation. Obtained data was analyzed using SPSS version 20.
Forty-one of the 120 subjects were RSV-positive and 13 (31.7%) of the RSV-positive children had bacteraemia. The clinical predictors of RSV-infection compared to the RSV-negative children were “infancy”[(p=0.039, OR= 3.154, 95% CI (1.160, 9.386)] and “conjunctivitis” [(p=0.018, OR = 5.097, 95% CI (1.320, 19.688). A comparison of clinical and radiographic features among RSV-positive without bacteraemia and those with bacteraemia was not significant (p> 0.05). However, all RSV-positive children with bacteraemia had an admission diagnosis of pneumonia while none of those with a diagnosis of bronchiolitis had bacteraemia (p=0.024).
It was concluded that clinical and radiographic features are poor predictors of bacteraemia in children with RSV infection. RSV-positive children with an admission diagnosis of pneumonia may however benefit from routine antibiotic therapy while those with a diagnosis of bronchiolitis may not require routine antibiotics.
Host-directed therapy - New ways to curing infections
Biography: Zifeng Yang is an associate professor of Guangzhou Institute of Respiratory Disease (GIRS), The First Affiliated Hospital of Guangzhou Medical University. He graduated from Macau University of Science and Technology and worked at GIRS since 2006. He is a clinical virology scientist with particular interest in emerging virus disease at the animal-human interface including avian H7N9 and H5N6 influenza virus, and MERS-CoV as well as the associated viral immunology. His research interests also involve the use of pharmaceutical animal model (ie. Mice, ferrets and tree shrew) to understand the protective effect, optimized regimen and underlying mechanisms of approved drugs, novel compounds and traditional Chinese medicines against respiratory viruses.
Abstract: Influenza viruse has been thought a threat to public health, especially, highly pathogenic avian influenza H7N9 appeared in China since 2013 and mortality reach up to approximately 40% . However, High frequency resistance limit the clinical use of anti-influenza treatment and urgently need a novel therapeutic strategy. Laggera Pterodonta mainly distributed in Southwest of China is used to treat respiratory virus infection and other related diseases . A sesquiterpenoid Pterodontic acid was isolated from Laggera Pterodonta and had antiviral effect on H1N1 influenza virus through CPE inhibition assay, but its specific mechanism of treating influenza was indistinct. In this study, NF-κB luciferase report system and Quantitative real-time PCR were adopted for detecting the inhibition of Pterodontic acid to activation of NF-κB induced by H1N1 influenza virus and pro-inflammatory cytokines expression. The results showed that Pterodontic acid reduced the H1N1 influenza viral-induced activation of NF-κB pathway and cytokine expression (IL-6, MIP-1β, MCP-1 and IP-10) in a dose-dependent manner. The previous researches indicated that NF-κB played a key role in the process of influenza virus invading host. The inhibitor of NF-κB remarkably decreased the viral titer and viral-induced cytokine expression in vitro and vivo . Additionally, robust cytokine production (cytokine storm) is main reason that contribute to influenza infection-induced morbidity and mortality . Thus, Pterodontic acid from Laggera Pterodonta modulated the NF-κB signaling pathway resulted in reduction of influenza viral replication and overproduction of pro-inflammatory cytokines expression simultaneously. In future, this may supply a novel therapeutic strategy to influenza treatment.
Biography: Dr. Ming-Liang He is an associate professor in Department of Biomedical Sciences, City University of Hong Kong, China. Dr. He obtained his Ph.D degree in Shanghai Institute of Biochemistry and cell Biology, China in 1995, and obtained Postdoc. Training in Roswell Park Cancer Institute at Buffalo NY (1995-1997) and Washington University Scholl of medicine at St. Louis MO (1997-2000). He was appointed as assistant professor in The University of Hong Kong (2000-2004) and associate professor in The Chinese University of Hong Kong (2005-2015). Dr. He focuses on antiviral research and virus-host interactions.
Abstract: Enterovirus 71 (EV71), a member of the Picornaviridae family, is a non-enveloped single-stranded RNA virus. It is the major causative agent of repeated outbreaks of hand, foot and mouth disease (HFMD). In severe cases, especially those among in infants and children, EV71 infection causes severe neurological complications such as aseptic meningitis, brain stem encephalitis, pulmonary edema, poliomyelitis-like paralysis and eventual death. In the last decade, the continuous outbreaks of EV71 in Asia-Pacific region have caused considerable deaths. More than 7 million HFMD cases were reported in China between 2008 and 2012, of which 2457 were fatal. No effective antiviral drug is currently used for treating EV71 infection.
Traditional Chinese herbs are great resources for novel antiviral compounds. Here we report that Oblongifolin M (OM), an active compound isolated from Garcinia oblongifolia, potently inhibited EV71 infection in a dose dependent manner. To identify its potential effectors in the host cells, we successfully identified 18 proteins from 52 differentially expressed spots by comparative proteomics studies. Further studies showed that knockdown of ERp57 inhibited viral replication through downregulating viral IRES (internal ribosome entry site) activities, whereas ectopic expression of ERp57 increased IRES activity and partly rescued the inhibitory effects of OM on viral replication. Knockout of ERp57 by CRISPR-Cas9 almost completelyabolished EV71 reproduction. We demonstrated that OM is an effective antiviral agent; and that ERp57 is one of its cellular effectors against EV71 infection. (supported by RGC-GRF of HKSAR, No. 11100215, No.14105214; and NSFC No. 81471964, No. 81671995).
Biography: Dr. Gloria Ramirez-Nieto, got her degree on Veterinary Medicine from Universidad Nacional de Colombia, she has an MSc on Veterinary Microbiology from the Royal Veterinary College, University of London and completed her Ph.D from University of Maryland working on avian influenza virus. She is associated professor at Universidad Nacional de Colombia, Bogotá. Her professional career has been devoted to teaching and research on the virology field. Her main focus of interest is related to the molecular characterization, host-pathogen interactions and pathogenesis of viral diseases with emphasis on those with a great impact on animal health and public health.
Abstract: Swine influenza viruses (SIV) are considered important and endemic pathogens in the pig population worldwide. Major losses associated to weight gain reduction and respiratory signs are very common. Circulation of SIV classical strains was demonstrated in the late 70’s in Colombia but only until 2008 and later on after emergence of the 2009 Pandemic H1N1 (H1N1pdm09) isolates were obtained from field samples in Colombia. Emergence of new influenza viruses and molecular variation traits pose relevance in understanding epidemiology of SIV. To contribute to the knowledge of SIV infections we collected and analyzed 801 lung tissue samples during 2015-2017 from slaughterhouse pigs in 11 different regions in Colombia. These samples were processed and analyzed by qRT-PCR for detection of Influenza A virus matrix gene and further assays were performed for subtyping. Positive samples were prepared for isolation trials, using SPF embryo chicken eggs and MDCK cells. Full length sequencing of HA, NA, M y NS genes of the virus isolates was conducted. The results of this study demonstrated molecular detection of SIV in lung samples from slaughterhouse pigs in 5 geographical regions, corresponding to the main raising pig areas in Colombia. The results indicate that the virus remains as a subclinical infection that can be exacerbated by several conditions in the farm. This type of samples need to be considered as an alternative to accomplish comprehensive molecular and epidemiological studies as it was possible no only to detect but also to isolate SIV. The phylogenetic analysis of the virus isolates showed a relationship with human origin H1N1pdm09 strains from different countries, including Colombia. Accordingly, human contact represents an important source for transmission of influenza viruses into pig populations. These results highlight the importance in designing surveillance strategies, in order to reduce the epidemiological risk on the animal-human interface associated with influenza virus infections
Immunology/animal models in Virology
Biography: Yadira Lobaina Mato has a PhD in Biological Sciences and a position as senior researcher.
In 1999 she graduated of Biochemistry, with Honors, at Havana University. Since this year up to now she works in the Vaccine Division at the Center for Genetic Engineering and Biotechnology from Havana, Cuba. In 2011 she finished a Master Degree in New Trends of Contemporary Biotechnology, mention in Development of Biomedical Products. She has experience in the expression and purification of recombinant proteins, in immunology based research studies, and in the evaluation of vaccine candidates in animal models and clinical trials. She has also experience in the evaluation of adjuvants and mucosal immunization routes. She has worked in research projects related with the development of new vaccines against Neisseria meningitides, HIV, and mainly therapeutic vaccines against chronic hepatitis B. She has published more than 25 research and review articles. During her career she has received five awards from the National Academy of Sciences. She is member of the Cuban Society of Immunology and the Cuban Society of Pharmacology. In 2016 she was selected to participate in the Advanced Course of Vaccinology (ADVAC17th) auspicated by Merieux Foundation.
Abstract: Introduction: Chronic hepatitis B is a major health problem, with more than 350 million people infected worldwide. Available therapies have limited efficacy and require long-term treatments. A mucosal approach for chronic hepatitis B immunotherapy has been tested in preclinical and clinical studies using a novel vaccine formulation comprising the surface and core virus like particles from hepatitis B virus (HBV).
Materials and Methods: The therapeutic vaccine candidate comprised two recombinant HBV antigens: HBsAg and HBcAg. Several preclinical studies including immuno-toxicological evaluations using HBsAg transgenic mice have been completed. Until now four clinical trials concluded including a phase III trial.
Results: The vaccine candidate was very immunogenic in mice after intranasal or combined administrations inducing higher antibody titers, potent proliferative responses and the secretion of gamma interferon by spleen cells. The formulation also demonstrated its safety in toxicological studies. Several clinical trials phase I to III, conducted in two countries, evidenced the safety and efficacy of the vaccine candidate.
Conclusions: The obtained results support the future introduction of this product in the clinical practice. To our knowledge, this is the first therapeutic approach exploiting mucosal route against a chronic infectious disease to reach phase III clinical trial.
Biography: Akinori Takaoka graduated from Sapporo Medical University School of Medicine in 1992, and gained his Ph.D. and M.D. at the same university in 1996. He worked as a post-doctoral fellow and a Research Associate at the Department of Immunology, Graduate School of Medicine & Faculty of Medicine, at University of Tokyo. In this department he was appointed as an Assistant Professor in 2000 and Lecturer in 2002. Then, he was appointed Professor of Hokkaido university in 2007. Since 2012, he had been Director of the Institute for Genetic Medicine for four years.
Abstract: The aryl hydrocarbon receptor (AHR) has been known to be a receptor for xenobiotics such as dioxins and mostly studied in terms of its toxic effects on development, cell proliferation, and immune responses. On the other hand, recent studies have identified endogenous ligands, which activate AHR-mediated signalings to regulate biological events including immune responses. However, its molecular mechanisms remained poorly understood. Recently, we demonstrated a novel role of constitutive AHR-mediated signaling in type I interferon (IFN) response during viral infection. We found that type I IFN induction in response to infection with various types of virus such as influenza virus (FluV) and herpes simplex virus was remarkably enhanced in AHR deficient cells or mice, as compared with the wild-type. Consistently, the viral titers of the bronchoalveolar lavage fluid were reduced in AHR deficient mice after intranasal infection with FluV. In addition, type I IFN pathway activated by nucleic acid sensors such as RIG-I, MDA5, and cGAS/STING was also significantly upregulated in AHR deficient cells. These results suggest that AHR activation by endogenous AHR ligand(s) may negatively regulate type I IFN induction during viral infection. In fact, a consistent result was also obtained upon treatment with CH-223191, an AHR-specific antagonist. Next, we tried to find how AHR regulates IFN response, and identified TIPARP (TCDD-inducible poly(ADP-ribose)polymerase) as one of the AHR-inducible genes, which negatively regulated type I IFN response. As we expected, Tiparp-deficient cells showed significantly increased levels of IFN-beta production following FluV infection, which was accompanied with marked suppression of viral replication. Further analyses demonstrated that TIPARP ADP-ribosylated TBK1, a pivotal kinase for IFN pathway, suppressing the TBK1 kinase activity. In addition, CH-223191 antagonist did not show any more effect on IFN-beta production by FluV infection in the absence of TIPARP. Thus, our results show that AHR-signaling activated by endogenous ligand(s), such as kynurenine, modulates type I IFN antiviral response. In addition, it has been shown that this negative regulation of IFN response is based at least upon the ADP-ribosylation of TBK1 by AHR-inducible TIPARP, which is a hitherto-unrecognized posttranslational modification of TBK1 protein. The AHR-TIPARP pathway may represent a potential therapeutic target for the control of viral infection.
Biography: Waqas Ahmad have recently joined the post of Assistant Professor in the Section of Epidemiology and Public Health, University of Veterinary and Animal Sciences subcampus, Jhang, Pakistan. I have been engaged in rabies virus neuropathology since the last 5 years including the work of my master and PhD studies. The later one I did from Institute of Zoonosis, Jilin University, China. My publications mainly cover the mechanism of rabies virus infection inside neuronal cells aspects of rabies virus.
Abstract: Rabies virus (RABV) manifests strong affinity for the nervous system where it causes neuronal dysfunction, and alters the structural morphology of dendritic spines by inducing changes in cytoskeleton which comprises of actin, microtubule and intermediate filaments. For microtubule, EB3 is a microtubule plus-end binding protein that stabilizes microfilaments and belongs to the third family member of RP/EB group. The p140cap is an interacting partner of EB3 that together with EB3 plays vital role in postsynaptic density, dendritic spine functions and morphology. The gene expression and respective protein contents of EB3 and p140cap were compared in neuronal cells under the effect of fixed and street strain of RABV. Furthermore, gene expression levels of important actin binding, microtubule and synapse related proteins were also studied.
In this study, immunofluorescence, western blot and real time PCR were carried out to compare the gene expression and corresponding protein contents of different cytoskeleton related proteins. Both strains of RABV significantly reduced the gene expression and protein contents of EB3 and p140cap. However, the street strain considerably inhibited the transcription level of p140cap, but had no significant effect on its protein level. The fixed strain produced fractured microtubules in fixed neurons, and down-regulated different microtubule and actin associated proteins, while up-regulated the level of Tesk2. In neuronal cells, the fluorescence localisation of EB3 protein was random and varied at 48 hour and 98 hours of post-infection.
Like other neurodegenerative diseases, Rabies may possibly alter the neuronal structures by changing the gene expression levels of integral protein binding partners of microtubules and actin. Most importantly, EB3 and p140cap are vital in maintaining the morphology of dendritic spine. The results could be utilized to envisage other neurological diseases by explaining the intricate relationship between EB3 and p140cap in dendritic spines.
Age-specific Immune Response to Vaccination
Biography: Jacques Choucair is in Department of Infectious Diseases,, Hôtel-Dieu de France, Beirut, Lebanon
Abstract: To assess, in non vaccinated healthy adults, the response to the standard protocol SP of vaccination for hepatitis B(0, 1, 6 months), and the response to two protocols using additional boosters in those who remain non-responders.
192 employees of the Psychiatric Hospital of the Cross with a mean age of 44.3 (44.3±12.35), non vaccinated and not having other illness(hepatic failure, chronic renal failure, HIV infection, cancer and activehepatitis), are vaccinated with Engerix B (Engerix® B 20 µg/1 ml) by the SP. The non-responders to this protocol (anti-Hbs antibodies <10UI/l) are divided into two groups. The first group receives a single booster (R1) 4 months after the SP, and those who remained non-responders receive a double booster (R1b) 2 years after the SP. The second group (P2) receives a unique double booster (R2), 2 years after the SP.
The rate of response after the vaccination by the SP is 75.5 %( 145/192).
28 non-responders (P1) receive a booster R1 after 4 months; their rate of response is 32.14 %( 9/28). The 19 non-responders to R1 receive a double booster (R1b) after 2 years. Their rate of response is 36.84 %( 7/19). The rate of response among the group P1 is 57.14 %( 16/28).
19 non-responders (P2) receive a unique double booster after 2 years. Their rate of response is 63.16 %( 12/19).
9.9 %( 19/192) of individuals don't respond to any of the boosters. The rate of response decreases with the age. This decrease is 5% every year and 41% every 10 years.
For the same age, men are 2 fold more responders then women. After receiving all boosters, there is no difference between genders.
A unique double booster done 2years after the SP gives a better response then a single booster done after 4 months, and a similar response to a single booster done after 4 months followed by a double booster done after 2 years. The female gender and the age are 2 factors that decrease the response to the vaccination.
Keywords: hepatitis B, vaccination, booster, non-responders
Biography: Zaki Eisa Omar is Head of Virology and Molecular Diagnosis, King Fahd Hospital, Jazan, Saudi Arabia.
Abstract: A molecular study was conducted to investigate the prevalence of Hepatitis C
virus genotypes in HCV infected population of Jazan, Saudi Arabia. Samples were collected between February 2010 and March 2013 from all hepatitis C patients. Of the 198 studied participants. 36(18.2%) of them were infected with 1a, 27(13.6%) with 1b, 6(3.0%) with 2 and 9(4.5%) with genotype 3 of hepatitis C. Mixed infection was found in 9 patients [1&4 in 9(4.5%). The most prevalent genotype was 3a with rate of 50% followed by genotype 3b and 1a, respectively. Nine samples remained untyped, suggesting the need of further investigation of genotypes in this region. It has been proposed that sequencing of these samples may be helpful to reveal these genotypes and further epidemiology of HCV genotypes.