Porcine Picornavirus 3C Protease Degrades PRDX6 to Impair PRDX6-mediated Antiviral Function  

作　　者：Congcong Wang Huanhuan Feng Xiangle Zhang Kangli Li Fan Yang Weijun Cao Huisheng Liu Lili Gao Zhaoning Xue Xiangtao Liu Zixiang Zhu Haixue Zheng 

机构地区：[1]State Key Laboratory of Veterinary Etiological Biology,OIE/National Foot and Mouth Diseases Reference Laboratory,Key Laboratory of Animal Virology of Ministry of Agriculture,Lanzhou Veterinary Research Institute,Chinese Academy of Agricultural Sciences,Lanzhou 730046,China

出　　处：《Virologica Sinica》2021年第5期948-957,共10页中国病毒学（英文版）

基　　金：supported by grants from the National Key R&D Program of China(2017YFD0501103);the Key Development and Research Foundation of Yunnan(2018BB004);the Chinese Academy of Agricultural Science and Technology Innovation Project(Y2017JC55);Central Public-interest Scientific Institution Basal Research Fund(1610312016013 and 1610312017003)。

摘　　要：Peroxiredoxin-6(PRDX6)is an antioxidant enzyme with both the activities of peroxidase and phospholipase A2(PLA2),which is involved in regulation of many cellular reactions.However,the function of PRDX6 during virus infection remains unknown.In this study,we found that the abundance of PRDX6 protein was dramatically decreased in foot-and-mouth disease virus(FMDV)infected cells.Overexpression of PRDX6 inhibited FMDV replication.In contrast,knockdown of PRDX6 expression promoted FMDV replication,suggesting an antiviral role of PRDX6.To explore whether the activity of peroxidase and PLA2 was associated with PRDX6-mediated antiviral function,a specific inhibitor of PLA2(MJ33)and a specific inhibitor of peroxidase activity(mercaptosuccinate)were used to treat the cells before FMDV infection.The results showed that incubation of MJ33 but not mercaptosuccinate promoted FMDV replication.Meanwhile,overexpression of PRDX6 slightly enhanced type I interferon signaling.We further determined that the viral 3Cprowas responsible for degradation of PRDX6,and 3Cpro-induced reduction of PRDX6 was independent of the proteasome,lysosome,and caspase pathways.The protease activity of 3Cprowas required for induction of PRDX6 reduction.Besides,PRDX6 suppressed the replication of another porcine picornavirus Senecavirus A(SVA),and the 3Cproof SVA induced the reduction of PRDX6 through its proteolytic activity as well.Together,our results suggested that PRDX6 plays an important antiviral role during porcine picornavirus infection,and the viral 3Cproinduces the degradation of PRDX6 to overcome PRDX6-mediated antiviral function.

关 键 词：Porcine picornavirus Peroxiredoxin-6(PRDX6) 3Cpro Phospholipase A2(PLA2) ANTAGONISM 

分 类 号：S852.65[农业科学—基础兽医学]