title: Differential restriction of human immunodeficiency virus type 2 and simian immunodeficiency virus SIVmac by TRIM5alpha alleles.
abstract: Primate lentiviruses have narrow host ranges, due in part to their sensitivities to mammalian intracellular antiviral factors such as APOBEC3G and TRIM5alpha. Despite the protection provided by this innate immune system, retroviruses are able to transfer between species where they can cause disease. This is true for sooty mangabey simian immunodeficiency virus, which has transferred to humans as HIV-2 and to rhesus macaques as SIVmac, where it causes AIDS. Here we examine the sensitivities of the closely related HIV-2 and SIVmac to restriction by TRIM5alpha. We show that rhesus TRIM5alpha can restrict HIV-2 but not the closely related SIVmac. SIVmac has not completely escaped TRIM5alpha, as shown by its sensitivity to distantly related TRIM5alpha from the New World squirrel monkey. Squirrel monkey TRIM5alpha blocks SIVmac infection after DNA synthesis and is not saturable with restriction-sensitive virus-like particles. We map the determinant for TRIM5alpha sensitivity to the structure in the capsid protein that recruits CypA into HIV-1 virions. We also make an SIV, mutated at this site, which bypasses restriction in all cells tested.
authors.affiliation: Wohl Virion Center, Division of Infection and Immunity, Windeyer Building, University College London, 46 Cleveland St., London W1T4JF, United Kingdom.
authors.forename: Laura M J
authors.initials: LM
authors.lastname: Ylinen
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Keckesova
authors.forename: Sam J
authors.initials: SJ
authors.lastname: Wilson
authors.forename: Srinika
authors.initials: S
authors.lastname: Ranasinghe
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Towers
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000090103:Antiviral Restriction Factors; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology*; D002415:Cats; D002460:Cell Line; D021984:Cyclophilin A / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics; D005814:Genes, Viral; D015498:HIV-2 / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009154:Mutation; D011506:Proteins / Q000235:genetics* / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics; D012453:Saimiri; D017386:Sequence Homology, Amino Acid; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D013045:Species Specificity; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D014774:Virulence
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D004279:DNA, Viral; D011506:Proteins; D034741:RNA, Small Interfering; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases; D021984:Cyclophilin A