Chaimayo C, et al. Specificity and functional interplay between influenza virus PA-X and NS1 shutoff activity. PLoS Pathog. 2018 Nov 29;14(11):e1007465
Influenza A viruses modulate host antiviral responses to promote viral growth and pathogenicity. Through viral PA-X and NS1 proteins, the virus is capable of suppressing host protein synthesis, termed "host shutoff." Although both proteins are known to induce general shutoff, specificity of target genes and their functional interplay in mediating host shutoff are not fully elucidated. In this study, we generated four recombinant influenza A/California/04/2009 (pH1N1) viruses containing mutations affecting the expression of active PA-X and NS1. We analyzed viral growth, general shutoff activity, specificity of mRNA targets, and viral gene expressions. Our results showed that PA-X was the major contributor in reducing general host protein expression in the virus-infected cells. Intriguingly, our transcriptomic analysis from infected human airway A549 cells indicate that shutoff-active NS1 specifically targeted host mRNAs related to interferon (IFN) signaling pathways and cytokine release. Specificity of target mRNAs was less evident in PA-X, although it preferentially degraded genes associated with cellular protein metabolism and protein repair. Interestingly, in the presence of shutoff-active NS1, PA-X also degraded viral mRNAs, especially NS segments. The virus expressing shutoff-active NS1 with reduced amount of PA-X expression most efficiently suppressed antiviral and innate immune responses in human cells, indicating that influenza virus needs to optimize the contribution of these two shutoff proteins to circumvent host responses for its optimum growth.
See Also:
Latest articles in those days:
- The evolution, complexity, and diversity of swine influenza viruses in China: A hidden public health threat 2 days ago
- MHC class II proteins mediate sialic acid independent entry of human and avian H2N2 influenza A viruses 2 days ago
- Histopathologic Features and Viral Antigen Distribution of H5N1 Highly Pathogenic Avian Influenza Virus Clade 2.3.4.4b from the 2022–2023 Outbreak in Iowa Wild Birds 2 days ago
- Detection and characterization of H5N1 HPAIV in environmental samples from a dairy farm 2 days ago
- Genomic Characterization of Highly Pathogenic Avian Influenza A H5N1 Virus Newly Emerged in Dairy Cattle 2 days ago
[Go Top] [Close Window]