Avian influenza viruses suppress innate immunity by inducing trans-transcriptional readthrough via SSU72

Autor: Yan Zhao, Fengming Huang, Zhen Zou, Yuhai Bi, Yang Yang, Cong Zhang, Qiang Liu, Daozhen Shang, Yiwu Yan, Xiangwu Ju, Song Mei, Peng Xie, Xiao Li, Mingyao Tian, Shuguang Tan, Huijun Lu, Zongsheng Han, Kangtai Liu, Yuqing Zhang, Junbo Liang, Zhu Liang, Qingchao Zhang, Jiahui Chang, William J. Liu, Cong Feng, Tanshi Li, Michael Q. Zhang, Xiaoyue Wang, George F. Gao, Yingxia Liu, Ningyi Jin, Chengyu Jiang
Rok vydání: 2022
Předmět:
Zdroj: Cellular & Molecular Immunology. 19:702-714
ISSN: 2042-0226
Popis: Innate immunity plays critical antiviral roles. The highly virulent avian influenza viruses (AIVs) H5N1, H7N9, and H5N6 can better escape host innate immune responses than the less virulent seasonal H1N1 virus. Here, we report a mechanism by which transcriptional readthrough (TRT)-mediated suppression of innate immunity occurs post AIV infection. By using cell lines, mouse lungs, and patient PBMCs, we showed that genes on the complementary strand (“trans” genes) influenced by TRT were involved in the disruption of host antiviral responses during AIV infection. The trans-TRT enhanced viral lethality, and TRT abolishment increased cell viability and STAT1/2 expression. The viral NS1 protein directly bound to SSU72, and degradation of SSU72 induced TRT. SSU72 overexpression reduced TRT and alleviated mouse lung injury. Our results suggest that AIVs infection induce TRT by reducing SSU72 expression, thereby impairing host immune responses, a molecular mechanism acting through the NS1-SSU72-trans-TRT-STAT1/2 axis. Thus, restoration of SSU72 expression might be a potential strategy for preventing AIV pandemics.
Databáze: OpenAIRE
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