CYCLOPHILIN A MODULATES PROCESSING OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 P55(GAG) - MECHANISM FOR ANTIVIRAL EFFECTS OF CYCLOSPORINE-A

The molecular chaperone cyclophilin A (Cyp A) modulates human immunode ficiency virus type 1 (HIV-1) infectivity through its interactions wit h Gag structural proteins. The molecular mechanism for CypA in HIV-1 r eplication is not known. We studied chaperone effects on Gag precursor processing using cyclosporin A (CsA) to bind CypA and prevent its int eraction with p55(Gag). CsA treatment inhibited p55(Gag) processing in extracellular virus-like particles produced from COS cells. We confir med the effect of CsA on Gag processing by examining virions produced from CEMx174 cells infected with HIV-1(LAI). Particles accumulated in the presence of CsA displayed mostly immature virion morphology and la cked condensed capsids. CsA has a direct effect on HIV-1 Gag processin g that implicates CypA as having an important role in the maturation o f HIV-I particles. (C) 1998 Academic Press.