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

作　　者：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 JLiu Cong Feng Tanshi Li Michael Q.Zhang Xiaoyue Wang George FGao Yingxia Liu Ningyi Jin Chengyu Jiang 

机构地区：[1]State Key Laboratory of Medical Molecular Biology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,Department of Biochemistry,Peking Union Medical College,Beijing 100005,China [2]Shenzhen Key Laboratory of Pathogen and Immunity,State Key Discipline of Infectious Disease,Second Hospital Affiliated with Southern University of Science and Technology,Shenzhen Third People’s Hospital,Shenzhen,Guangdong 518112,China [3]CAS Key Laboratory of Pathogenic Microbiology and Immunology,Institute of Microbiology,Center for Influenza Research and Early-warning(CASCIRE),CAS-TWAS Center of Excellence for Emerging Infectious Diseases(CEEID),Chinese Academy of Sciences,Beijing 100101,China [4]School of Life Science,University of Science and Technology of China,Hefei,Anhui 230027,China [5]Department of Automation,Tsinghua University,Beijing 100084,China [6]Genetic Engineering Laboratory,Institute of Military Veterinary,Academy of Military Medical Sciences,Changchun,Jilin 130062,China [7]State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy,West China Hospital,Sichuan University,Chengdu,Sichuan 610000,China [8]State Key Laboratory of Medical Molecular Biology,Department of Biochemistry and Center for Bioinformatics,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,School of Basic Medicine,Peking Union Medical College,Beijing 100005,China [9]National Institute for Viral Disease Control and Prevention,Chinese Centers for Disease Control and Prevention,Beijing 102206,China [10]Department of Emergency,General Hospital of the PLA,Haidian District,Beijing 100853,China [11]Department of Biological Sciences and Center for Systems Biology,The University of Texas at Dallas,Richardson,TX,USA

出　　处：《Cellular & Molecular Immunology》2022年第6期702-714,共13页中国免疫学杂志（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(NSFC)(81788101,31870163,and 32100104);the CAMS Innovation Fund for Medical Sciences(2021-I2M-1-022);the Strategic Priority Research Program of the Chinese Academy of Sciences(CAS)(XDB29010102);CAS Southest Asia Biodiversity Research Institute(151C53KYSB20210023);Beijing Natural Science Foundation(L192007);National Pathogen Resource Center,and State Key Laboratory Special Fund(2060204);Y.B.is supported by the NSFC Outstanding Young Scholars(31822055);Youth Innovation Promotion Association of the CAS(2017122 and Y2021034);Overseas Expertise Introduction Center for Discipline Innovation(“111 Center”)(BP0820029).

摘　　要：Innate immunity plays critical antiviral roles. The highly virulent avian influenza viruses (AIVs) H5N1, H7N9, and H5N6 can betterescape host innate immune responses than the less virulent seasonal H1N1 virus. Here, we report a mechanism by whichtranscriptional readthrough (TRT)-mediated suppression of innate immunity occurs post AIV infection. By using cell lines, mouselungs, and patient PBMCs, we showed that genes on the complementary strand (“trans” genes) influenced by TRT were involved inthe disruption of host antiviral responses during AIV infection. The trans-TRT enhanced viral lethality, and TRT abolishmentincreased cell viability and STAT1/2 expression. The viral NS1 protein directly bound to SSU72, and degradation of SSU72 inducedTRT. SSU72 overexpression reduced TRT and alleviated mouse lung injury. Our results suggest that AIVs infection induce TRT byreducing 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.

关 键 词：AIV infection TRT SSU72 NS1 Immune escape 

分 类 号：R392[医药卫生—免疫学]