Day 2 :
XENOTOX Inc, USA
Keynote: A decade later, another look at what role in global spread of H5N1 played upregulation by host cell dioxin of gene encoding type A influenza virus NS1 binding protein
Time : 10:00 - 10:35
Ilya B. Tsyrlov, M.D., Ph.D., D.Sci., has completed his PhD at the age of 27 years from Novosibirsk University and postdoctoral studies from Leningrad Academy of Medical Sciences. He is the President and Chief Scientific Officer of XENOTOX, Inc., an American premier biomedical innovation organization. He has published 4 monographs and about 250 papers in reputed journals and has been serving as an editorial board member of several jornals
Cognate DRE sites within DNA enhancer epitomizes wide range of mammalian genes expression mediated via the Ah receptor pathway. Earlier we postulated the same for DRE-containing viral genes transactivation caused by dioxin in human cells infected with HIV-1, HBV and HCMV. Here, such mechanistic concept applied to type A influenza virus NS1 binding protein in human and avian (G. gallus gallus) host cells. The NS1 is known to prevent transcriptional induction of antiviral interferons, to inhibit splicing and dsRNA-mediated signal transduction in target cells. Presenting data range from the cellular to population levels. It was shown that gene encoding the NS1 possessed multiple DREs (core nucleotide sequence 3' A-CGCAC 5'), two of which were identified within the promoter area, namely at positions -7942 and -687. SITECON, an established computational tool for detecting transcriptional factor binding site recognition, proved the above sites as potentially active. SITECON-selected adjacent variable sequences were used to detect properties of the DRE site, and conformational similiarity score threshold of 0.95 was utilized to rank identified DRE. On the cellular level, Western blot analysis of lysates of infected or DNA-transfected confluent HeLa cells pretreated with 10 ppt dioxin for 36 h revealed several-fold increase of NS1-specific polypeptide. As the NS1 promoter contains two potentially active DRE, an extrapolation from the data on HIV-1 (1 DRE) and HCMV (10 DRE) also suggests that concentration of dioxin upregulating NS1 gene should be moderately above current dioxin levels in general population (~ 4 ppt). Presumably, elevated dioxin level in the host cells might lead to enhanced ability of NS1 to diminish antiviral interferons. That can bring new insights to the fact that resistance of highly virulent H5N1 to antiviral effects of IFN-ß and TNF-alpha directly associated with the NS1. On the population level, the data on wild birds and domestic poultry (G. gallus gallus) dying from H5N1 in Guangdong province of China, and Long An, Tieng Giang and Ben Tre provinces of Vietnam, all relate to the fact that water and soil in these regions are highly contaminated with dioxin-like compounds. Eventually, human cohorts from the above regions of China and Vietnam are exposed to elevated concentrations of dioxin, which might serve as a promotional factor for seasonal influenza outbreaks. Moreover, the sub-nanomolar body burden dioxin might strongly facilitate spreading of the H5N1 in case avian flu pandemic were to occur.
Michigan State University, USA
Time : 10:50 - 11:25
Reza Nassiri is Associate Dean of Global Health; Director of Institute of International Health; Professor of Clinical Pharmacology, Professor of Family and Community Medicine, and lecturer in Global Health, Infectious Diseases and Tropical Medicine at Michigan State University College of Osteopathic Medicine. His research interests focuses on Clinical Pharmacology of HIV/AIDS & TB, prevention and control of infectious diseases, neglected tropical diseases, community health, global health, and socio-ethical determinants of health. Prof. Nassiri works on international public health issues and has expertise in global health education, research, policy and governance. He has made contributions in various fields of medical sciences including clinical investigation and health education. One the basis of his extensive experience and expertise in HIV/AIDS and TB, he developed Clinical Research Programs in Brazil, South Africa, Haiti, Dominican Republic and Mexico. The core foci of such programs are socio-cultural, bio-ethical determinant of HIV/AIDS and TB prevention, control, and intervention.
About 75 recently emerging infectious diseases that affect humans are caused by various zoonotic pathogens including influenza viruses such as H1N1, H5N1, and H7N9. Pandemic influenza outbreaks significantly highlights about the role of One Health (OH) approach where expertise in human, animal, and environmental health combines together with multidisciplinary strategies solve interrelated problems to adapt effective collaboration, communication, management and evidenced-based preventive measures. Avian and Swine flu are examples of global health concern that justify exploring the role of OH enhancing optimal preventive outcome and to promptly disseminate epidemiologic data sharing among various stakeholders including academic institutions that are traditionally well equipped to collaborate with the internal and external stakeholders, especially in areas such as human, veterinary, and laboratory surveillance practices. The human-animal-ecosystem interface plays a critical role in spread of emerging and re-emerging infectious disease including influenza viruses. As the world population is rising especially urban populations, we are facing an increase in poultry and swine populations globally by necessity, and therefore, increased in the frequency of zoonotic influenza viruses’ infections among human populations is more likely. One Health approach which is formulated to mitigate and curb public health best practice for the triple threats, can result in direct benefits in human health. Furthermore, adaptation and incorporation of such approach will significantly impact preventive measures as well as identification of risk factor and risk assessment. Major health organizations, such as the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), the US Institute of Medicine (IOM), and the European Centers for Disease Control have unanimously concluded that that more action and information on influenza transmission and prevention is internationally critical to pandemic planning and management. Human health is directly and inextricably linked to the health of animals and ecosystem and influenza viruses are no exception to this pivotal link. One Health collaborations and implementations can help to effectively minimize the burden of disease including economic burden. Therefore, improving international public health infrastructure for zoonotic disease control and prevention through OH approach provides advantages and benefits in controlling zoonotic diseases caused by influenza viruses.