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 viru...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.展开更多
基金supported by the National Natural Science Foundation of China(92369104,82271790,92169113)the Beijing Natural Science Foundation(JQ23028,7212067)+4 种基金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.
文摘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.
