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

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.

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

Correction to:Virologica Sinica(2021)36:948-957 https://doi.org/10.1007/s12250-021-00352-4 Due to our negligence,the original version of this article,published online on March 15,2021,contained a mistake in Figure 2E(The Knockdown band of Western blotting was provided incorrectly).The correct Fig.2E is given below.We apologize for this error and state that this does not change the scientific conclusions of the article in any way.