title: Chimeric human immunodeficiency virus type 1 (HIV-1) virions containing HIV-2 or simian immunodeficiency virus Nef are resistant to cyclosporine treatment.
abstract: The viral protein Nef and the cellular factor cyclophilin A are both required for full infectivity of human immunodeficiency virus type 1 (HIV-1) virions. In contrast, HIV-2 and simian immunodeficiency virus (SIV) do not incorporate cyclophilin A into virions or need it for full infectivity. Since Nef and cyclophilin A appear to act in similar ways on postentry events, we determined whether chimeric HIV-1 virions that contained either HIV-2 or SIV Nef would have a direct effect on cyclophilin A dependence. Our results show that chimeric HIV-1 virions containing either HIV-2 or SIV Nef are resistant to treatment by cyclosporine and enhance the infectivity of virions with mutations in the cyclophilin A binding loop of Gag. Amino acids at the C terminus of HIV-2 and SIV are necessary for inducing cyclosporine resistance. However, transferring these amino acids to the C terminus of HIV-1 Nef is insufficient to induce cyclosporine resistance in HIV-1. These results suggest that HIV-2 and SIV Nef are able to compensate for the need for cyclophilin A for full infectivity and that amino acids present at the C termini of these proteins are important for this function.
authors.affiliation: Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, Georgia 30310, USA.
authors.forename: Mahfuz
authors.initials: M
authors.lastname: Khan
authors.forename: Lingling
authors.initials: L
authors.lastname: Jin
authors.forename: Ming Bo
authors.initials: MB
authors.lastname: Huang
authors.forename: Lesa
authors.initials: L
authors.lastname: Miles
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Bond
authors.forename: Michael D
authors.initials: MD
authors.lastname: Powell
mesh_terms: D000595:Amino Acid Sequence; D021984:Cyclophilin A / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000235:genetics; D015693:Gene Products, nef / Q000737:chemistry / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D015498:HIV-2 / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry / Q000235:genetics*; D014771:Virion / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D015693:Gene Products, nef; C429284:NEF protein, SIV; D054334:Viral Regulatory and Accessory Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D016572:Cyclosporine; D021984:Cyclophilin A