Depletion of endogenous CypA increased influenza virus infectivity, whereas overexpression of CypA decreased infectivity and inhibited the translocation of M1 protein into the nucleus.
Does Cyclophilin A interact with Influenza A virus M1 protein and affect viral replication?
Cyclophilin A interacts with the Influenza A virus M1 protein, impairing the early stage of viral replication by inhibiting M1 translocation into the nucleus.
Influenza A virus matrix protein (M1) is the most abundant conservative protein that regulates the replication, assembly and budding of the viral particles upon infection. Several host cell factors have been determined to interact with M1 possibly in regulating influenza virus replication. By yeast two-hybrid screening, the isomerase cyclophilin A (CypA) was identified to interact with the M1 protein. CypA specifically interacted with M1 both in vitro and in vivo. The mutagenesis results showed CypA bound to the functional middle (M) domain of M1. The depletion of endogenous CypA by RNA interference resulted in the increase of influenza virus infectivity while overexpression of CypA caused decreasing the infectivity in affected cells. The immunofluorescence assays indicated that overexpressed CypA deduced the infectivity and inhibited the translocation of M1 protein into the nucleus while did not affect nucleoprotein entering the nucleus. Further studies indicated that overexpression of CypA significantly increased M1 self-association. Western blot with purified virions confirmed that CypA was encapsidated within the virus particle. These results together indicated that CypA interacted with the M1 protein and affected the early stage of the viral replication.
Liu et al. (Thu,) conducted a other in Influenza A virus infection. Cyclophilin A (CypA) depletion or overexpression vs. Control cells was evaluated on Viral infectivity and M1 protein translocation. Depletion of endogenous CypA increased influenza virus infectivity, whereas overexpression of CypA decreased infectivity and inhibited the translocation of M1 protein into the nucleus.