title: Disruption of human TRIM5alpha antiviral activity by nonhuman primate orthologues.
abstract: TRIM5 is a determinant of species-specific differences in susceptibility to infection by retroviruses bearing particular capsids. Human immunodeficiency virus type 1 (HIV-1) infection is blocked by the alpha isoform of macaque TRIM5 (TRIM5alpha(rh)) or by the product of the owl monkey TRIM5-cyclophilin A gene fusion (TRIMCyp). Human TRIM5alpha potently restricts specific strains of murine leukemia virus (N-MLV) but has only a modest effect on HIV-1. The amino termini of TRIM5 orthologues are highly conserved and possess a coiled-coil domain that promotes homomultimerization. Here we show that heterologous expression of TRIM5alpha(rh) or TRIMCyp in human cells interferes with the anti-N-MLV activity of endogenous human TRIM5alpha (TRIM5alpha(hu)). Deletion of the cyclophilin domain from TRIMCyp has no effect on heteromultimerization or colocalization with TRIM5alpha(hu) but prevents interference with anti-N-MLV activity. These data demonstrate that TRIM5 orthologues form heteromultimers and indicate that C-terminal extensions alter virus recognition by multimers of these proteins.
authors.affiliation: Department of Microbiology, Columbia University College of Physicians and Surgeons, 701 West 168th St., New York, NY 10032, USA.
authors.forename: Lionel
authors.initials: L
authors.lastname: Berthoux
authors.forename: Sarah
authors.initials: S
authors.lastname: Sebastian
authors.forename: David M
authors.initials: DM
authors.lastname: Sayah
authors.forename: Jeremy
authors.initials: J
authors.lastname: Luban
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D000090103:Antiviral Restriction Factors; D016645:Aotidae / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D021984:Cyclophilin A / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity; D000882:Haplorhini / Q000378:metabolism*; D006801:Humans; D009052:Leukemia Virus, Murine / Q000187:drug effects* / Q000472:pathogenicity; D008253:Macaca mulatta / Q000378:metabolism; D051379:Mice; D011506:Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D000998:Antiviral Agents; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases; D021984:Cyclophilin A