Oishi Kohei, Yamayoshi Seiya, Kawaoka Yoshihiro
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, United States.
Front Microbiol. 2019 Mar 6;10:432. doi: 10.3389/fmicb.2019.00432. eCollection 2019.
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.
流感病毒蛋白PA-X通过抑制宿主蛋白表达来调节宿主免疫反应和病毒致病性。N端区域的核酸内切酶活性位点、C端PA-X特异性区域的碱性氨基酸簇以及NatB对PA-X的N端乙酰化对于PA-X的关闭活性很重要。在这里，我们聚焦于源自A/California/04/2009和A/WSN/33病毒的PA-X的关闭活性，因为这两种PA-X蛋白在关闭活性方面存在差异。诱变分析表明，分别位于28位和65位的脯氨酸和丝氨酸在这种差异中起核心作用。此外，我们发现P28和S65也影响源自其他流感病毒亚型的PA-X的关闭活性。这些数据表明，P28和S65有助于增强PA-X的关闭活性。
