The TET3 inflammasome senses unique long HSV-1 proteins for virus particle budding from the nucleus  

作　　者：Qiannv Liu Weitao Li Yan Qian Chunlei Wang Chun Kong Mengqian Li Liangliang Sun Lang Sun Yanli Pang Changtao Jiang Shuo Wang Pengyan Xia 

机构地区：[1]Department of Immunology,School of Basic Medical Sciences,Peking University,Bejing 100191,China [2]NHC Key Laboratory of Medical Immunology,Peking University,Bejing 100191,China [3]Key Laboratory of Molecular Immunology,Chinese Academy of Medical Sciences,Beijing 100191,China [4]State Key Laboratory of Female Fertility Preservation,Center for Reproductive Medicine,Department of Obstetrics and Gynecology,Peking University Third Hospital,Beijing 100191,China [5]National Clinical Research Center for Obstetrics and Gynecology,Peking University Third Hospital,Beijing 100191,China [6]Department of Physiology and Pathophysiology,School of Basic Medical Sciences,State Key Laboratory of Vascular Homeostasis and Remodeling,Peking University,Beijing 100191,China [7]Center for Obesity and Metabolic Disease Research,School of Basic Medical Sciences,Peking University,Beijing 100191,China [8]CAS Key Laboratory of Pathogen Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences,100101 Bejing,China

出　　处：《Cellular & Molecular Immunology》2024年第11期1322-1334,共13页中国免疫学杂志(英文版)

基　　金：supported by the National Natural Science Foundation of China(92369104,82271790,92169113);the Beijing Natural Science Foundation(JQ23028,7212067);the National Key R&D Program of China(2021YFA1300202,2022YFC2302900);the Strategic Priority Research Programs of the Chinese Academy of Sciences(XDB29020000);the Key Research Program of Frontier Sciences of Chinese Academy of Sciences(ZDBS-LY-SM025);the CAS Project for Young Scientists in Basic Research(YSBR-010);the Fok Ying Tung Education Foundation to P.X.,the Youth Innovation Promotion Association of CAS to S.W.

摘　　要：Inflammasomes play important roles in resisting infections caused by various pathogens.HSV-1 is a highly contagious virus among humans.The process by which HSV-1 particles bud from the nucleus is unique to herpes viruses,but the specific mechanism is still unclear.Here,we screened genes involved in HSV-1 replication.We found that TET3 plays an essential role in HSV-1 infection.TET3 recognizes the UL proteins of HSV-1 and,upon activation,can directly bind to caspase-1 to activate an ASC-independent inflammasome in the nucleus.The subsequent cleavage of GSDMD in the nucleus is crucial for the budding of HSV-1 particles from the nucleus.Inhibiting the perforation ability of GSDMD on the nuclear membrane can significantly reduce the maturation and spread of HSV-1.Our results may provide a new approach for the treatment of HSV-1 in the future.

关 键 词：HSV-1 unique long proteins TET3 ASC-independent inflammasome 

分 类 号：R28[医药卫生—中药学]