Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/45019
Title: Specificity and functional interplay between influenza virus PA-X and NS1 shutoff activity
Authors: Chutikarn Chaimayo
Megan Dunagan
Tsuyoshi Hayashi
Netty Santoso
Toru Takimoto
University of Rochester Medical Center
Faculty of Medicine, Siriraj Hospital, Mahidol University
Ohio State University
National Institutes of Biomedical Innovation
Keywords: Biochemistry, Genetics and Molecular Biology;Immunology and Microbiology
Issue Date: 1-Nov-2018
Citation: PLoS Pathogens. Vol.14, No.11 (2018)
Abstract: © 2018 Chaimayo et al. http://creativecommons.org/licenses/by/4.0/. 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.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85058084682&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/45019
ISSN: 15537374
15537366
Appears in Collections:Scopus 2018

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