E K Franke

Human immunodeficiency virus type 1 Gag protein binds to cyclophilins A and B

Retroviral Gag protein is capable of directing the assembly of virion particles independent of other retroviral elements and plays an important role early in the infection of a cell. Using the GAL4 two hybrid system, we screened a cDNA expression library and identified two host proteins, cyclophillins (CyPs) A and B, which interact specifically with the human immunodeficiency virus type 1 (HIV-1) Gag polyprotein Pr55gag. Glutathione S-transferase-CyP fusion proteins bind tightly to Pr55gag in vitro, as well as to the HIV-1 capsid protein p24. Cyclosporin A efficiently disrupts the Gag-CyPA interaction and less efficiently disrupts the Gag-CyPB interaction. The Gag-CyP interaction may be important for the HIV-1 life cycle and may be relevant to the pathology caused by this immunosuppressive virus.

Cyclophilin and Gag in HIV-1 Replication and Pathogenesis

The gag gene products perform many functions in the retroviral life cycle. Recent work suggests that specific binding of HIV-1 Gag to the cellular proteins known as the cyclophilins is necessary for viral infectivity and perhaps of importance to the immunopathology associated with HIV infection. Cyclophilins are ubiquitous prolyl isomerases thought to function as chaperones. Members of this family of proteins are required for the immunosuppression induced by cyclosporin A and are suspected regulators of cellular activation pathways. Here we review the functions of the gag proteins, what is known about the Gag-cyclophilin interaction, and the possible relevence of this interaction for HIV-1 replication and pathogenesis.