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Volume 4, Issue 6(Suppl) J Infect Dis Ther
ISSN: 2332-0877 JIDT, an open access journal Influenza 2016
September 12-13, 2016
Page 36
Notes:
conferenceseries.com
Influenza
September 12-13, 2016 Berlin, Germany
2nd International Conference on
Ilya B Tsyrlov, J Infect Dis Ther 2016, 4:6(Suppl)
Adecade later, another look at what role in global spread of H5N1 played up-regulation by host cell dioxin of gene
encoding type A influenza virus NS1 binding protein
C ognate 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
similarity 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 hours 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 up-regulating 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-β and TNF-alpha directly associated with the NS1. On the population level, the data on wild birds
and domestic poultry (G. gallus gallus) dying fromH5N1 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.
Biography
Ilya B Tsyrlov has completed his PhD 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 journals.
Ilya B Tsyrlov
XENOTOX Inc., USA