Cyclophilin A restricts influenza A virus replication through degradation of the M1 protein

Cyclophilin A (CypA) is a typical member of the Cyclophilin family of peptidyl-prolyl isomerases and is involved in the replication of several viruses. Previous studies indicate that CypA interacts with Influenza Virus M1 protein and impairs the early stage of the viral replication. To further understand the molecular mechanism by which CypA impairs Influenza Virus replication, a 293T cell line depleted for endogenous CypA was established. The results indicated that CypA inhibited the initiation of virus replication. In addition, the infectivity of Influenza Virus increased in the absence of CypA. Further studies indicated that CypA had no effect on the stages of virus genome replication or transcription and also did not impair the nuclear export of the viral mRNA. However, CypA decreased the viral protein level. Additional studies indicated that CypA enhanced the degradation of M1 through the ubiquitin/proteasome-dependent pathway. Our results suggest that CypA restricts Influenza Virus replication through accelerating degradation of the M1 protein.