Cyclophilin a modulates processing of human immunodeficiency virus type 1 p55Gag: mechanism for antiviral effects of cyclosporin A.
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 p55Gag. CsA treatment inhibited p55Gag 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-1LAI. 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.
Streblow
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DN
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison 53706, USA.
Kitabwalla
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M
Malkovsky
M
M
Pauza
C D
CD
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D019556:COS Cells; D016572:Cyclosporine / Q000494:pharmacology*; D015683:Gene Products, gag / Q000096:biosynthesis*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D014176:Protein Biosynthesis / Q000187:drug effects; D011498:Protein Precursors / Q000096:biosynthesis*; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology
D000998:Antiviral Agents; D015683:Gene Products, gag; D011498:Protein Precursors; C059767:p55 gag precursor protein, Human immunodeficiency virus 1; D016572:Cyclosporine