The Influences of Avian Influenza Viruses NS1 Protein on Viral Replication, Host Adaptation and the Immune Response

Autor: Wen-Chien Wang, 王文謙
Rok vydání: 2018
Druh dokumentu: 學位論文 ; thesis
Popis: 106
Avian influenza viruses (AIVs) cause a significant poultry disease worldwide. In the last three decades, H6N1 virus has been confirmed in Taiwan. Since the initial outbreaks of Mexican-like H5N2 low pathogenic avian influenza virus (LPAIV) in 2003, a variety of H5N2 AIVs emerged these years, including Mexican-like H5N2 high pathogenic avian influenza virus (HPAIV) H5N2 viruses in 2008, H5N2, H5N3, H5N8 AIVs of clade 2.3.4.4 in 2015 and H5N6 AIVs in 2017. All of them show different characteristics in virulence and host range. In the current study, sequence alignment revealed high frequency of sequence variations among the non-structural 1 (NS1) of AIVs in Taiwan. Influenza virus NS1 protein involves in limiting innate immune responses and regarded as one of the host range determinants. Therefore, the goal of this study was set to explore the roles of NS1 protein in host adaptation and in viral virulence of these emerging AIVs. To address this issue, a series of reassorted viruses carrying the NS segments of different Taiwanese AIVs were generated in the backbone of a H6N1 AIV by reverse genetics. Growth kinetics in DF-1 and MDCK cells showed the diversity of NS1 protein makes differences in AIV replication between mammalian and avian cells. Then, the expressing levels of cytokines in AIV infected DF-1, Duck embryo (DE) and A549 cells were measured. Some reassorted viruses resulted in significant differences of cytokine expression at 6 hours post infection in cells and embryos and indicated that high expression level of innate immunity cytokines may correlate with poor viral replication in cells and embryos. Expression levels of cytokines in chicken embryos were similar to the results of DF-1 cells, whereas most of reassorted viruses induced high expression levels of cytokines in duck embryos and DE cells. In conclusion, NS1 variants affect the growth kinetics, innate immune responses and cytokine expressions, and these differences could be responsible for the different characteristics of AIVs in Taiwan.
Databáze: Networked Digital Library of Theses & Dissertations
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