Novel activities of cyclophilin A and cyclosporin A during HIV-1 infection of primary lymphocytes and macrophages.
Studies conducted in cell lines indicate that cyclophilin A (CypA) is a component of HIV type 1 (HIV-1) virions, and that when CypA incorporation into virions is inhibited by treatment of infected cells with the immunosuppressive agent cyclosporin A (CsA), HIV-1 infection also is inhibited. Because HIV-1 particles assemble along a different pathway and incorporate different host proteins in macrophages than in other cell types, we investigated CypA and CsA activities in HIV-1-infected primary human macrophages, compared with primary human lymphocytes. We tested virus protein production, virion composition and infectivity, and progress through the virus life cycle under perturbation by drug treatment or mutagenesis in infected cells from multiple donors. Our findings from both primary cell types are different from that previously reported in transformed cells and show that the amount of CypA incorporated into virions is variable and that CsA inhibits HIV-1 infection at both early and late phases of virus replication, the stage affected is determined by the sequence of HIV-1 Gag. Because the cell type infected determines the identity of host proteins active in HIV-1 replication and can influence the activity of some viral inhibitors, infection of transformed cells may not recapitulate infection of the native targets of HIV-1.
Saini
Manisha
M
Molecular Virology Division, St. Luke's-Roosevelt Hospital Center, Columbia University Medical Center, 432 West 58th Street, New York, NY 10019, USA.
Potash
Mary Jane
MJ
D019380:Anti-HIV Agents / Q000494:pharmacology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral / Q000187:drug effects / Q000276:immunology; D021984:Cyclophilin A / Q000378:metabolism / Q000502:physiology*; D016572:Cyclosporine / Q000378:metabolism / Q000494:pharmacology*; D015683:Gene Products, gag / Q000378:metabolism / Q000502:physiology; D016655:HIV Core Protein p24 / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000201:enzymology / Q000821:virology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000821:virology*; D017354:Point Mutation; D014771:Virion / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology
D019380:Anti-HIV Agents; D015683:Gene Products, gag; D016655:HIV Core Protein p24; D016572:Cyclosporine; D021984:Cyclophilin A