Gag protein from human immunodeficiency virus type 1 assembles in the absence of cyclophilin A.
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 (Streblow et al., 1998. Virology 245, 197-202). We now use in vitro translation and physical analysis of Gag structures to refine our understanding of how cyclophilin A affects HIV-1 replication. Gag assembled into oligomeric structures in vitro in 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.
Streblow
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Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison 53706, USA.
Kitabwalla
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Pauza
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D000818:Animals; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D016572:Cyclosporine / Q000378:metabolism; D019281:Dimerization; D015683:Gene Products, gag / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D014176:Protein Biosynthesis; D011487:Protein Conformation; D011817:Rabbits; D014158:Transcription, Genetic; D019065:Virus Assembly; D014779:Virus Replication
D015683:Gene Products, gag; D016572:Cyclosporine; D019696:Peptidylprolyl Isomerase