HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GAG PROTEIN BINDS TO CYCLOPHILIN-A AND CYCLOPHILIN-B

Retroviral Gag protein is capable of directing the assembly of virion particles independent of other retroviral elements and plays an import ant role early in the infection of a cell. Using the GAL4 two hybrid s ystem, we screened a cDNA expression library and identified two host p roteins, cyclophilins (CyPs) A and B, which interact specifically with the human immunodeficiency virus type 1 (HIV-1) Gag polyprotein Pr55g ag. Glutathione S-transferase-CyP fusion proteins bind tightly to Pr55 gag in vitro, as well as to the HIV-1 capsid protein p24. Cyclosporin A efficiently disrupts the Gag-CyPA interaction and less efficiently d isrupts the Gag-CyPB interaction. The Gag-CyP interaction may be impor tant for the HIV-1 life cycle and may be relevant to the pathology cau sed by this immunosuppressive virus.