CYCLOPHILIN-A IS REQUIRED FOR AN EARLY STEP IN THE LIFE-CYCLE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 BEFORE THE INITIATION OF REVERSE TRANSCRIPTION

Cyclophilin A (CyPA) is incorporated into human immunodeficiency virus type 1 (HIV-1) virions via contact with the Gag polyprotein. Genetic or pharmacologic disruption of CyPA incorporation causes a quantitativ e reduction in virion infectivity with no discernible effects on virio n assembly or on endogenous reverse transcriptase activity. Instead, t he reduction of virion-associated CyPA is accompanied by a parallel, q uantitative decrease in the initiation of viral DNA synthesis after in fection of T cells. The infectivity of CyPA deficient virions is not r estored by pseudotyping with Env of amphotropic murine leukemia virus, demonstrating that CyPA is not required for the HIV-1-Env-CD3 interac tion. These results indicate that CyPA is required for an early step i n the HIV-1 life cycle following receptor binding and membrane fusion but preceding reverse transcription. CyPA is the first cellular protei n other than the cell surface receptor shown to be required for an ear ly event in the life cycle of a retrovirus.