title: Short communication: high natural polymorphism in the gag gene cleavage sites of non-B HIV type 1 isolates from Gabon.
abstract: The main goal of the present study was to determine the frequency of substitutions in the cleavage sites (CS) of gag gene among non-B HIV-1 isolates from Gabon. Fifty plasma specimens, collected in 2010-2011, from HIV-1-infected patients failing first-line antiretroviral (ARV) regimens (constituted of two nucleoside reverse transcriptase inhibitors+one nonnucleoside reverse transcriptase inhibitor) (n=38) and from HIV-1-infected individuals untreated with ARV (n=12) were analyzed in the gag and gag-pol cleavage sites. Compared to HXB2 reference sequence, the total median number of substitutions in gag and gag-pol CS was 10 (range, 5-18). The cleavage site p2/NC was the most variable of the four gag CS with 100% (50/50) isolates carrying at least 1 substitution (range, 1-9). The two gag-pol TFP/p6pol and p6pol/PR CS sites were also highly variable (at least one substitution, 50/50, 100% in both cases). Substitutions at position G381 (p2/NC), L449 (p1/p6gag), and K444 (TFP/p6pol) were significantly more frequent in CRF02_AG strains, compared to other non-B strains (30.4% vs. 3.7%, p=0.03; 87.0% vs. 59.3%, p=0.03; and 91.3% vs. 59.3%, p=0.01, respectively). Other non-B subtypes were significantly more likely to harbor substitutions at position N487 (p6pol) (70.4%) than CRF02_AG (39.1%) (p=0.02). In Gabon, gag and gag-pol cleavage sites were highly polymorphic in protease inhibitor-naive patients harboring non-B HIV-1 strains. In sub-Saharan Africa, further studies are definitively required to better understand the impact of gag mutations among subjects receiving second-line LPV/r-containing regimens (monotherapy or triple combinations).
authors.affiliation: Laboratoire de Rétrovirologie, CIRMF, BP769, Franceville, Gabon.
authors.forename: Florian
authors.initials: F
authors.lastname: Liégeois
authors.forename: Dorine Gaëlle Ikanga
authors.initials: DG
authors.lastname: Reteno
authors.forename: Augustin
authors.initials: A
authors.lastname: Mouinga-Ondémé
authors.forename: Jeanne
authors.initials: J
authors.lastname: Sica
authors.forename: François
authors.initials: F
authors.lastname: Rouet
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D005681:Gabon; D015750:Genes, gag / Q000235:genetics*; D015751:Genes, pol; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic
chemical_list: D044966:Anti-Retroviral Agents