The Impacts of Reassortant Avian Influenza H5N2 Virus NS1 Proteins on Viral Compatibility and Regulation of Immune Responses

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.

Genetic Characterization and Pathogenesis of Three Novel Reassortant H5N2 Viruses in South Korea, 2018

“…According to the phylogenetic tree, 6/8 genes of these three H5N2 AIVs were donated from Korean strains. The phylogenetic tree also reveals two different reassortment events in the NS gene segment, which may be a critical factor responsible for viral replication as reported previously [57]. All gene segments of KNU18-28 and KNU18-86 were donated from the same virus strains in the reassortment event.…”

Eugenol-Functionalized Magnetite Nanoparticles Modulate Virulence and Persistence in Pseudomonas aeruginosa Clinical Strains

“…However, our results reveal that NPs could potentiate the effect of eugenol on persister population selection, highlighting the utility of hybrid nanosystems, based on natural products and inorganic NPs, to reduce the selection of resistant cells under antibiotic pressure. This field is currently under intense investigation, with different categories of alternative agents, such as antimicrobial peptides [ 28 ], and other natural agents, such as phenol-soluble modulins, being proposed [ 43 ].…”

The orf virus (ORFV) protein OV20.0 interacts with the microprocessor complex subunit DGCR8 to regulate miRNA biogenesis and ORFV infection

“…Influenza virus (A/Puerto Rico/8/1934) was propagated in embryonic eggs. Cells were infected by influenza virus at an MOI of 0.1 for 1 h, and were subsequently cultured in DMEM supplemented with 1 μg mL −1 of TPCK‐treated trypsin for 24 or 48 h. Viral yield was determined by plaque assay in MDCK cells [22].…”