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The Effects Of Avian Influenza NS1 Protein On Interferon Promoter Activation

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Title: The Effects Of Avian Influenza NS1 Protein On Interferon Promoter Activation
Author(s): Pająk, Daria Anna
Contributor: University of Helsinki, Faculty of Biological and Environmental Sciences
Degree program: Master's Programme in Genetics and Molecular Biosciences
Specialisation: Molecular and analytical health biosciences study track
Language: English
Acceptance year: 2020
Influenza A viruses are pathogens infecting birds and selected mammals. They are responsible for around 500 000 human deaths each year and pose a substantial economic burden to the healthcare system. The most important pathway in influenza virus detection is a retinoic acid-inducible gene I pathway, which recognizes the 5’-triphosphate in viral RNA. Its activation leads to the production of interferons: a group of cytokines important in overcoming viral infection. In order to replicate successfully, viruses had to develop mechanisms to overcome host defences. They include, among others, regulation of interferons and interferon stimulated genes expression. During influenza A virus infection, this function is performed by viral non-structural protein 1 (NS1). The aim of this study was evaluating the effect of NS1 of five different avian influenza strains and one seasonal influenza strain on activation of type I and III interferon gene promoters. The NS1 of seasonal virus H3N2 shown the highest suppression of both interferon I and III promoters, while NS1 originating from avian H9N2 and H7N7 strains had limited effect on interferon promoter activation. NS1 of H5N1/04, H5N1/97 and H7N9 was very effective at suppressing interferon type I promoter, which correlates with the severity of the infection in humans. When it comes to interferon type III promoter, H7N9 was very efficient at the suppression, while NS1 of H5N1/04 had little impact on promoter activation. The study has provided more information on the efficiency of potentially pandemic avian influenza strains at inhibition of interferon response and may be a base for further research. The project was conducted at the Finnish Institute of Health and Welfare.
Keyword(s): avian influenza H5N1 H7N9 H9N2 H7N7 H3N2 interferons RIG-I NS1

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