title: Significant changes in integrase-associated HIV-1 replication capacity between early and late isolates.
abstract: During the human immunodeficiency virus type 1 (HIV-1) pandemic, continuous, extensive genetic diversification of the virus has been observed. To study the effect of HIV-1 diversification on integrase-associated viral replication capacity (RC), 94 HIV-1 subtype B integrase sequences from two groups of antiretroviral-naive viruses isolated 15 y apart were amplified and recombined with an HIV-1 infectious clone. Viral RC was determined by infecting a T cell line with a long terminal repeat-driven green fluorescent protein reporter. Significant differences in integrase-mediated RC were observed between recombinant viruses from early and late isolates (p=0.0286). Integrases from late isolates had significantly lower sequence conservation scores compared to an ancestral subtype B sequence (p<0.0001). Integrase amino acid polymorphisms S17N, I72V, S119P, and D256E were associated with a lower ex vivo viral RC. These results suggest that integrase sequence diversification has affected ex vivo HIV-1 RC.
authors.affiliation: Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona 08916, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Capel
authors.forename: Mariona
authors.initials: M
authors.lastname: Parera
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Martínez
mesh_terms: D019943:Amino Acid Substitution; D002460:Cell Line; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D015658:HIV Infections / Q000821:virology*; D019427:HIV Integrase / Q000235:genetics / Q000378:metabolism*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000821:virology; D014779:Virus Replication
chemical_list: D049452:Green Fluorescent Proteins; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1
keywords: Diversification; Fitness; HIV; Integrase