Mink enteritis virus infection induced cell cycle arrest and autophagy for its replication.

Mink enteritis virus (MEV) is an important pathogen causing mink viral enteritis. The mechanisms of cell cycle arrest induced by MEV infection and the roles of autophagy in MEV replication remain unclear. In this study, the roles of MEV NS1 protein in inducing cell cycle arrest were investigated, using the in vitro CRFK cell models. As a result, MEV infection increased the proportion of the cells in S phase, inducing S phase arrest. MEV NS1 protein also led to cycle arrest in S phase. And the deletions of NLS and TAD significantly weakened the ability of NS1 protein to cause cycle arrest in S phase, and NLS and TAD were the indispensable domains of NS1 protein. Furthermore, proteome profiling of the cells infected with MEV at the early stage demonstrated that the autophagy-related protein TRIM23 was significantly up-regulated during MEV infection. To investigate the effects of TRIM23 on MEV replication, the cell models were established, using siRNAs targeting TRIM23. The knockdown of TRIM23 resulted in the decreases in the levels of TBK1 protein and the phosphorylated p62 protein, and an increase in the level of p62 protein in the cells infected with MEV, indirectly influencing virus replication. The findings implied that S phase arrest and the up-regulated TRIM23 induced by MEV infection played the important roles in MEV replication.