Abstract
Avian influenza virus (AIV) can cause severe diseases in poultry worldwide. H6N1 AIV was the dominant enzootic subtype in 1985 in the chicken farms of Taiwan until the initial outbreak of a low pathogenic avian influenza (LPAI) H5N2 virus in 2003; thereafter, this and other LPAIs have been sporadically detected. In 2015, the outbreak of three novel H5Nx viruses of highly pathogenic avian influenza (HPAI) emerged and devastated Taiwanese chicken and waterfowl industries. The mechanism of variation in pathogenicity among these viruses is unclear; but, in light of the many biological functions of viral non-structural protein 1 (NS1), including interferon (IFN) antagonist and host range determinant, we hypothesized that NS genetic diversity contributes to AIV pathogenesis. To determine the impact of NS1 variants on viral infection dynamics, we established a reverse genetics system with the genetic backbone of the enzootic Taiwanese H6N1 for generation of reassortant AIVs carrying exogenous NS segments of three different Taiwanese H5N2 strains. We observed distinct cellular distributions of NS1 among the reassortant viruses. Moreover, exchange of the NS segment significantly influenced growth kinetics and induction of cytokines [IFN-α, IFN-β, and tumor necrosis factor alpha (TNF-α)] in an NS1- and host-specific manner. The impact of NS1 variants on viral replication appears related to their synergic effects on viral RNA-dependent RNA polymerase activity and IFN response. With these approaches, we revealed that NS1 is a key factor responsible for the diverse characteristics of AIVs in Taiwan.
Highlights
Avian influenza virus (AIV) causes highly contagious diseases in poultry worldwide and poses a severe public health threat to humans (Shi et al, 2016)
Previous studies have demonstrated that exchange of NS segments affects viral replication, pathogenicity, and host adaptation in highly pathogenic avian influenza (HPAI) viruses (HPAIVs) (Ma et al, 2010); and deletion of non-structural protein 1 (NS1) attenuates the virulence of H5N1 viruses (Steel et al, 2009; Shi et al, 2016)
Note, the four representative viruses were classified into distinct clades; eight genetic segments of NS0702 originated from the endemic H6N1 virus isolated in 2013, the same year as the HPAI H5N2 A/chicken/Taiwan/1680/2013 (NS1680); whereas A/chicken/Taiwan/683/2012 (NS683) and A/goose/Taiwan/01031/2015 (NS1031) originated from the endemic Mexican-like HPAIV H5N2 isolated in 2012 and clade 2.3.4.4 H5N2 isolated in 2015, respectively (Supplementary Figure S1)
Summary
Avian influenza virus (AIV) causes highly contagious diseases in poultry worldwide and poses a severe public health threat to humans (Shi et al, 2016). For the last two decades, H6N1 has been the enzootic AIV subtype in Taiwanese chicken farms (Lu et al, 1985; Lee et al, 2006, 2014), until an outbreak of low pathogenic avian influenza (LPAI) H5N2 occurred in 2003, followed by a second wave in 2008 (Cheng et al, 2010) This H5N2 was a reassortant virus, with hemagglutinin (HA) and neuraminidase (NA) likely derived from a Mexican-like H5N2 and internal genes from the enzootic H6N1 lineage. Previous studies have demonstrated that exchange of NS segments affects viral replication, pathogenicity, and host adaptation in HPAI viruses (HPAIVs) (Ma et al, 2010); and deletion of NS1 attenuates the virulence of H5N1 viruses (Steel et al, 2009; Shi et al, 2016). The results demonstrated that NS gene substitution markedly affects viral growth kinetics and host cytokine expression in avian and mammalian cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
