Multiple anti-interferon actions of the influenza A virus NS1 protein (J Virology, 2007, 13:7011-7021)

報告日期: 2007/10/09
報告時間: 16:00/16:50
報告學生: 郭懿瑩
講評老師: 謝奇璋
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Multiple Anti-Interferon Actions of the Influenza A Virus NS1 Protein

Georg Kochs, Adolfo Garcı´a-Sastre, and Luis Martı´nez-Sobrido

J Virology, 2007, 13:7011-7021

Speaker: Yih-Ying Kuo

Commentator: Dr. Chi-Chang Shieh

Time: 16:00-16:50, Oct. 9, 2007

Place: Room 602

 

Abstract:

  The non-structural protein 1 of influenza A virus (NS1A) is a multifunctional protein subjected to genetic drifts or shifts to affect viral replication and pathogenicity. It can interact with dsRNA and a series of host proteins to operate several post-transcriptional and translational controls on the suppression of IFN-mediated antiviral responses. To understand the roles of strain-specific NS1As on their virulence and associated functional capacities in modulating cytokine resistance, particularly on (A) blocking the activation of IFN regulatory factor 3 (IRF3) and (B) blocking posttranscriptional processing of cellular mRNAs, the authors characterized the NS1A/INF interplay in cells infected with recombinant viruses harboring different NS1A genes from three H1N1 strains. They found that A/PR/8/34 NS1 has a strong capacity to inhibit IRF3 and activation of the IFN-b promoter but is unable to suppress expression of other cellular genes. In contrast, the NS1A proteins of A/Tx/36/91 and of A/BM/1/18, the virus that caused the Spanish influenza pandemic, caused suppression of additional cellular gene expression. These results strengthen the role of NS1A in circumventing the establishment of an IFN-induced antiviral state, allowing virus replication even in the presence of IFN. Most importantly, the capability of NS1A in blocking cellular gene expression was found to be dependent on a newly described NS1A domain critical for the interaction with the cleavage and polyadenylation specificity factor (CPSF) component of the cellular pre-mRNA processing machinery. This study demonstrated the differential capacity of strain-specific NS1A to suppress the antiviral host defense at multiple levels that may affect virus pathogenicity.

References:

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2. Basler, C. F., et. al. 2001. Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes. Proc. Natl. Acad. Sci. USA 98:2746–2751.