Gag Protein from Human Immunodeficiency Virus Type 1 Assembles in the Absence of Cyclophilin A

Abstract

Human immunodeficiency virus type 1 (HIV-1) replication requires coordinated activities of host and viral factors. We reported previously that interactions of the host factor cyclophilin A with HIV-1 Gag polyproteins affected Gag processing and maturation of virus particles (Streblowet al.,1998.Virology245, 197–202). We now usein vitrotranslation and physical analysis of Gag structures to refine our understanding of how cyclophilin A affects HIV-1 replication. Gag assembled into oligomeric structuresin vitroin the presence or absence of cyclophilin A, and proteins synthesized under the two conditions were equally susceptible to cleavage by exogenous HIV-1 protease. These and previous data show that Cyclophilin A is required at a step between Gag assembly and Gag processing/virion morphogenesis. Cyclophilin A may be required for Gag conformational changes subsequent to assembly, that are required for efficient dimerization and activation of the viral protease.