CELLS WITH HIGH CYCLOPHILIN-A CONTENT SUPPORT REPLICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GAG MUTANTS WITH DECREASED ABILITY TO INCORPORATE CYCLOPHILIN-A

Gag polyprotein-mediated incorporation of cellular cyclophilin A (CyPA ) into virions is essential for the formation of infectious human immu nodeficiency virus type 1 (HIV-1) virions. Either a point mutation in Gag (P222A) or drugs which bind CyPA decrease virion incorporation of CyPA and interfere with HIV-1 replication. We have found that lymphoid cells varied greatly in their CyPA content and that cells with high C yPA content supported the replication of P222A HIV-1 Gag mutants. Thes e experiments demonstrated that a higher cellular CyPA content of some cells was able to compensate for the decreased binding affinity of P2 22A mutant Gag for CyPA, allowing virus replication to occur.