Cyclophilin A modulates processing of human immunodeficiency virus type 1 p55(Gag): Mechanism for antiviral effects of cyclosporin A

Abstract

The molecular chaperone cyclophilin A (Cyp A) modulates human immunodeficiency virus type 1 (HIV-1) infectivity through its interactions with Gag structural proteins. The molecular mechanism for CypA in HIV-1 replication is not known. We studied chaperone effects on Gag precursor processing using cyclosporin A (CsA) to bind CypA and prevent its interaction with p55(Gag). CsA treatment inhibited p55(Gag) processing in extracellular virus-like particles produced from COS cells. We confirmed the effect of CsA on Gag processing by examining virions produced from CEMx174 cells infected with HIV-1(LA1). Particles accumulated in the presence of CsA displayed mostly immature virion morphology and lacked condensed capsids. CsA has a direct effect on Hiv-1 Gag processing that implicates CypA as having an important role in the maturation of HIV-1 particles.