title: Susceptibility and adaptation to human TRIM5α alleles at positive selected sites in HIV-1 capsid.
abstract: Numerous in vitro studies attribute to human TRIM5α some modest anti-HIV-1 activity and human population studies suggest some differential effect of TRIM5α polymorphisms on disease progression. If the activity of TRIM5α were relevant in vivo, it could result in positive selection on the viral capsid. To address this issue, we identified 10 positively selected sites in HIV-1 capsid from multiple viral strains and generated 17 clade B viruses carrying a minor (i.e. low frequency) residue or an alanine at those positions. All recombinant viruses were susceptible to the modest effect of common human TRIM5α and allelic variants R136Q, and H419Y; H43Y and G249D TRIM5α were generally inactive. Increased sensitivity to TRIM5α was observed for some capsid variants, suggesting that minor residues are selected against in human populations. On the other hand, the modest potency of human TRIM5α does not translate in escape mutations in the viral capsid.
authors.affiliation: Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
authors.forename: Nadia
authors.initials: N
authors.lastname: Rahm
authors.forename: David
authors.initials: D
authors.lastname: Gfeller
authors.forename: Joke
authors.initials: J
authors.lastname: Snoeck
authors.forename: Raquel
authors.initials: R
authors.lastname: Martinez
authors.forename: Paul J
authors.initials: PJ
authors.lastname: McLaren
authors.forename: Millán
authors.initials: M
authors.lastname: Ortiz
authors.forename: Angela
authors.initials: A
authors.lastname: Ciuffi
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
mesh_terms: D000220:Adaptation, Biological; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D012641:Selection, Genetic; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D016655:HIV Core Protein p24; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases