数字农科院2.0

PA-X 122V Broadly Determines the Host Shutoff Activity of Influenza A Viruses

文献类型： 外文期刊

作者： Yuying Yang; Mengmeng Xu; Naixin Zhang; Qinhao Yu; Yunfei Wan; Chengzhi Xu; Yunpu Wu; Fei Meng; Yan Chen; Huanliang Yang; Guohua Deng; Jianzhong Shi; Li Jiang; Chuanling Qiao; Hualan Chen

关键词： Influenza A virus; PA-X protein; host shutoff; innate immune response

期刊名称： mBio

ISSN：

年卷期： 2025 年

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收录情况： SCIE（2025版）

摘要： Multiple genes are involved in the pathogenicity of influenza A virus. Our previous study reported two naturally occurring amino acid mutations in the polymerase acidic (PA) protein as crucial determinants of the virulence of Eurasian avian-like H1N1 (EA H1N1) influenza viruses. PA-X, an accessory protein encoded by the PA gene, is thought to play a role in viral pathogenicity and regulation of host immune response, but its specific function remains unclear. In this study, we found that two genetically similar EA H1N1 influenza viruses, A/swine/Liaoning/FX38/2017 (FX38) and A/swine/Liaoning/SY72/2018 (SY72), induced significantly different suppression levels of host protein synthesis. The difference in host shutoff activity induced by PA-X protein was the key factor affecting the inhibition of host gene expression. Loss of PA-X expression significantly reduced its host shutoff activity, thereby enhancing host antiviral immune response. PA-X deficiency had no apparent effect on polymerase activity or replication capacity. We pinpointed a single residue 122V involved in the ability of PA-X to inhibit host gene expression and thereby modulate the host antiviral response. Notably, PA-X 122V was highly conserved among multiple subtypes of influenza A viruses and vital for maintaining the inhibitory effects on the host protein synthesis. Together, these findings demonstrate that the PA-X protein plays a major role in the suppression of host protein synthesis during influenza virus infection, and elucidate the molecular mechanism by which the amino acid residue 122V in PA-X facilitates its suppression effects on host innate immune responses.

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