Identification of Amino Acid Residues in Influenza A Virus PA-X That Contribute to Enhanced Shutoff Activity

The influenza virus protein PA-X modulates the host immune responses and viral pathogenicity through suppression of host protein expression. The endonuclease active site in the N-terminal region, the basic amino acid cluster in the C-terminal PA-X-specific region, and N-terminal acetylation of PA-X...

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Main Authors:	Kohei Oishi, Seiya Yamayoshi, Yoshihiro Kawaoka
Format:	Article
Language:	English
Published:	Frontiers Media S.A. 2019-03-01
Series:	Frontiers in Microbiology
Subjects:	influenza A virus PA-X shutoff activity mutagenesis analysis mRNA degradation
Online Access:	https://www.frontiersin.org/article/10.3389/fmicb.2019.00432/full

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record_format	Article
spelling	doaj-f79de462ce78470da2b26a8780af6a132020-11-25T00:26:38ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-03-011010.3389/fmicb.2019.00432441056Identification of Amino Acid Residues in Influenza A Virus PA-X That Contribute to Enhanced Shutoff ActivityKohei Oishi0Seiya Yamayoshi1Yoshihiro Kawaoka2Yoshihiro Kawaoka3Yoshihiro Kawaoka4Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, JapanDivision of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, JapanDivision of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, JapanDepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin–Madison, Madison, WI, United StatesDepartment of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, JapanThe influenza virus protein PA-X modulates the host immune responses and viral pathogenicity through suppression of host protein expression. The endonuclease active site in the N-terminal region, the basic amino acid cluster in the C-terminal PA-X-specific region, and N-terminal acetylation of PA-X by NatB are important for the shutoff activity of PA-X. Here, we focused on the shutoff activity of PA-X derived from the A/California/04/2009 and A/WSN/33 viruses because these two PA-X proteins differ in their shutoff activity. Mutagenesis analysis revealed that proline and serine at positions 28 and 65, respectively, play a central role in this difference. Furthermore, we found that P28 and S65 also affect the shutoff activity of PA-X derived from other influenza virus subtypes. These data demonstrate that P28 and S65 contribute to enhanced shutoff activity of PA-X.https://www.frontiersin.org/article/10.3389/fmicb.2019.00432/fullinfluenza A virusPA-Xshutoff activitymutagenesis analysismRNA degradation
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Kohei Oishi Seiya Yamayoshi Yoshihiro Kawaoka Yoshihiro Kawaoka Yoshihiro Kawaoka
spellingShingle	Kohei Oishi Seiya Yamayoshi Yoshihiro Kawaoka Yoshihiro Kawaoka Yoshihiro Kawaoka Identification of Amino Acid Residues in Influenza A Virus PA-X That Contribute to Enhanced Shutoff Activity Frontiers in Microbiology influenza A virus PA-X shutoff activity mutagenesis analysis mRNA degradation
author_facet	Kohei Oishi Seiya Yamayoshi Yoshihiro Kawaoka Yoshihiro Kawaoka Yoshihiro Kawaoka
author_sort	Kohei Oishi
title	Identification of Amino Acid Residues in Influenza A Virus PA-X That Contribute to Enhanced Shutoff Activity
title_short	Identification of Amino Acid Residues in Influenza A Virus PA-X That Contribute to Enhanced Shutoff Activity
title_full	Identification of Amino Acid Residues in Influenza A Virus PA-X That Contribute to Enhanced Shutoff Activity
title_fullStr	Identification of Amino Acid Residues in Influenza A Virus PA-X That Contribute to Enhanced Shutoff Activity
title_full_unstemmed	Identification of Amino Acid Residues in Influenza A Virus PA-X That Contribute to Enhanced Shutoff Activity
title_sort	identification of amino acid residues in influenza a virus pa-x that contribute to enhanced shutoff activity
publisher	Frontiers Media S.A.
series	Frontiers in Microbiology
issn	1664-302X
publishDate	2019-03-01
description	The influenza virus protein PA-X modulates the host immune responses and viral pathogenicity through suppression of host protein expression. The endonuclease active site in the N-terminal region, the basic amino acid cluster in the C-terminal PA-X-specific region, and N-terminal acetylation of PA-X by NatB are important for the shutoff activity of PA-X. Here, we focused on the shutoff activity of PA-X derived from the A/California/04/2009 and A/WSN/33 viruses because these two PA-X proteins differ in their shutoff activity. Mutagenesis analysis revealed that proline and serine at positions 28 and 65, respectively, play a central role in this difference. Furthermore, we found that P28 and S65 also affect the shutoff activity of PA-X derived from other influenza virus subtypes. These data demonstrate that P28 and S65 contribute to enhanced shutoff activity of PA-X.
topic	influenza A virus PA-X shutoff activity mutagenesis analysis mRNA degradation
url	https://www.frontiersin.org/article/10.3389/fmicb.2019.00432/full
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Identification of Amino Acid Residues in Influenza A Virus PA-X That Contribute to Enhanced Shutoff Activity

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