Coronaviruses have developed various measures to evade innate immunity, We have previously shown that severe acute respiratory syndrome （SARS） coronavirus M protein suppresses type I interferon （IFN） production by...Coronaviruses have developed various measures to evade innate immunity, We have previously shown that severe acute respiratory syndrome （SARS） coronavirus M protein suppresses type I interferon （IFN） production by impeding the formation of functional TRAF3-containing complex. In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain （TM 1） located at the N terminus. M protein from human coronavirus HKU 1 does not inhibit IFN production. Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. TM 1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. Mechanistically, TM 1 is capable of binding with RIG-I, TRAF3, TBK1 and IKK~, and preventing the interaction of TRAF3 with its downstream effectors. Our work defines the molecular architecture of SARS coronavirus M orotein reouired for suooression of innate antiviral re^nnn^e.展开更多
Coronavirus(CoV)spillover originating from game animals,particularly pangolins,is currently a significant concern.Meanwhile,vigilance is urgently needed for coronaviruses carried by bats,which are known as natural res...Coronavirus(CoV)spillover originating from game animals,particularly pangolins,is currently a significant concern.Meanwhile,vigilance is urgently needed for coronaviruses carried by bats,which are known as natural reservoirs of many coronaviruses.In this study,we collected 729 anal swabs of 20 different bat species from nine locations in Yunnan and Guangdong provinces,southern China,in 2016 and 2017,and described the molecular characteristics and genetic diversity of alphacoronaviruses(αCoVs)and betacoronaviruses(βCoVs)found in these bats.Using RT-PCR,we identified 58(8.0%)bat CoVs in nine bat species from six locations.Furthermore,using the Illumina platform,we obtained two representative full-length genomes of the bat CoVs,namely TyRo-CoV-162275 and TyRo-CoV-162269.Sequence analysis showed that TyRo-CoV-162275 shared the highest identity with Malayan pangolin(Manis javanica)HKU4-related coronaviruses(MjHKU4r-CoVs)from Guangxi Province,whereas TyRo-CoV-162269 was closely related to HKU33-CoV discovered in a greater bamboo bat(Tylonycteris robustula)from Guizhou Province.Notably,TyRo-CoV-162275 has a putative furin protease cleavage site in its S protein and is likely to utilize human dipeptidyl peptidase-4(hDPP4)as a cell-entry receptor,similar to MERSCoV.To the best of our knowledge,this is the first report of a bat HKU4r-CoV strain containing a furin protease cleavage site.These findings expand our understanding of coronavirus geographic and host distributions.展开更多
文摘Coronaviruses have developed various measures to evade innate immunity, We have previously shown that severe acute respiratory syndrome （SARS） coronavirus M protein suppresses type I interferon （IFN） production by impeding the formation of functional TRAF3-containing complex. In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain （TM 1） located at the N terminus. M protein from human coronavirus HKU 1 does not inhibit IFN production. Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. TM 1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. Mechanistically, TM 1 is capable of binding with RIG-I, TRAF3, TBK1 and IKK~, and preventing the interaction of TRAF3 with its downstream effectors. Our work defines the molecular architecture of SARS coronavirus M orotein reouired for suooression of innate antiviral re^nnn^e.
基金the Special Foundation for the National Science and Technology Basic Research Program of China(2021FY100303)the Guangdong Provincial Science and Technology Program(2021B1212050021,2021B1212110003)+1 种基金the GDAS Special Project of Science and Technology Development(2021GDASYL-20210103052)the Young Top-notch Talent Cultivation Program of Hubei Province and the Youth Innovation Promotion Association of the Chinese Academy of Sciences(CAS)(2019328).
文摘Coronavirus(CoV)spillover originating from game animals,particularly pangolins,is currently a significant concern.Meanwhile,vigilance is urgently needed for coronaviruses carried by bats,which are known as natural reservoirs of many coronaviruses.In this study,we collected 729 anal swabs of 20 different bat species from nine locations in Yunnan and Guangdong provinces,southern China,in 2016 and 2017,and described the molecular characteristics and genetic diversity of alphacoronaviruses(αCoVs)and betacoronaviruses(βCoVs)found in these bats.Using RT-PCR,we identified 58(8.0%)bat CoVs in nine bat species from six locations.Furthermore,using the Illumina platform,we obtained two representative full-length genomes of the bat CoVs,namely TyRo-CoV-162275 and TyRo-CoV-162269.Sequence analysis showed that TyRo-CoV-162275 shared the highest identity with Malayan pangolin(Manis javanica)HKU4-related coronaviruses(MjHKU4r-CoVs)from Guangxi Province,whereas TyRo-CoV-162269 was closely related to HKU33-CoV discovered in a greater bamboo bat(Tylonycteris robustula)from Guizhou Province.Notably,TyRo-CoV-162275 has a putative furin protease cleavage site in its S protein and is likely to utilize human dipeptidyl peptidase-4(hDPP4)as a cell-entry receptor,similar to MERSCoV.To the best of our knowledge,this is the first report of a bat HKU4r-CoV strain containing a furin protease cleavage site.These findings expand our understanding of coronavirus geographic and host distributions.
