Polymorphisms occurring at the p6gag protein of HIV-1 have been previously found to have an impact on viral fitness and antiretroviral (ARV) resistance, mainly on subtype B genomes. We compared p6gag variability in a large group of 165 subtype F gag-pol sequences, with 36 subtype B sequences from the same study source, and identified sites of gag-pol coevolution under ARV selection pressure. Subtype-specific differences in the frequency of point mutations, insertions, and deletions previously associated with ARV resistance were found. Also, in our dataset of subtype F genomes a strong association between mutation P5L in the p1/p6 cleavage region of gag and the nelfinavir (NFV) resistance mutation N88DPR was found with no impact on the preference for any of the NFV resistance pathways.
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References
1.
HemelaarJ, GouwsE, GhysPD, OsmanovS. Global trends in molecular epidemiology of HIV-1 during 2000–2007. AIDS, 2011; 25,5:679–689.
2.
CarrJK, AvilaM, Gomez CarrilloMet al.Diverse BF recombinants have spread widely since the introduction of HIV-1 into South America. AIDS, 2001; 15:F41–F47.
3.
QuarleriJF, RubioA, CarobeneMet al.HIV type 1 BF recombinant strains exhibit different pol gene mosaic patterns: Descriptive analysis from 284 patients under treatment failure. AIDS Res Hum Retroviruses, 2004; 20:1100–1107.
4.
DilerniaDA, GomezAM, LourtauLet al.HIV type 1 genetic diversity surveillance among newly diagnosed individuals from 2003 to 2005 in Buenos Aires, Argentina. AIDS Res Hum Retroviruses, 2007; 23:1201–1207.
5.
AulicinoPC, BelloG, GuimaraesMLet al.Longitudinal analysis of HIV-1 BF1 recombinant strains in vertically infected children from Argentina reveals a decrease in CRF12_BF pol gene mosaic patterns and high diversity of BF unique recombinant forms. Infect Genet Evol, 2011; 11,2:349–357.
6.
Martinez-CajasJL, PaiMP, KleinMB, WainbergMA. Differences in resistance mutations among HIV-1 nonsubtype B infections: A systematic review of evidence (1996-2008)J Int AIDS Soc, 2009; 30:12–11.
7.
RheeSY, KantorR, KatzensteinDAet al.HIV-1 pol mutation frequency by subtype and treatment experience: Extension of the HIVseq program to seven non-B subtypes. AIDS, 2006; 20:643–651.
8.
AulicinoPC, RoccoCA, MecikovskyD, BolognaR, ManganoA, SenL. HIV type-1 genotypic resistance profiles in vertically infected patients from Argentina reveal an association between K103N+L100I and L74V mutations. Antivir Ther, 2010; 15,4:641–650.
9.
Ganser-PornillosBK, YeagerM, SundquistWI. The structural biology of HIV assembly. Curr Opin Struct Biol, 2008; 18,2:203–217.
10.
BallyF, MartinezR, PetersS, SudreP, TelentiA. Polymorphism of HIV type 1 gag p7/p1 and p1/p6 cleavage sites: Clinical significance and implications for resistance to protease inhibitors. AIDS Res Hum Retroviruses, 2000; 16,13:1209–1213.
11.
MarloweN, FlysT, HackettJJret al.Analysis of insertions and deletions in the gag p6 region of diverse HIV type 1 strains. AIDS Res Hum Retroviruses, 2004; 20,10:1119–1125.
12.
HolguínA, AlvarezA, SorianoV. Differences in the length of gag proteins among different HIV Type 1 subtypes. AIDS Res Hum Retroviruses, 2005; 21:886–893.
13.
MartinsAN, ArrudaMB, PiresAF, TanuriA, BrindeiroRM. Accumulation of P(T/S)AP late domain duplications in HIV Type 1 subtypes B, C, and F derived from individuals failing ARV therapy and ARV drug-naïve patients. AIDS Res Hum Retroviruses, 2011; 27,6:687–692.
14.
PetersS, MuñozM, YerlySet al.Resistance to nucleoside analog reverse transcriptase inhibitors mediated by human immunodeficiency virus type 1 p6 protein. J Virol, 2001; 75:9644–8653.
15.
SchneiderTD, StephensRM. Sequence logos: A new way to display consensus sequences. Nucleic Acids Res, 1990; 18:6097–6100.
16.
CrooksGE, HonG, ChandoniaJM, BrennerSE. WebLogo: A sequence logo generator. Genome Res, 2004; 14:1188–1190.
17.
VacicV, IakouchevaLM, RadivojacP. Two Sample Logo: A graphical representation of the differences between two sets of sequence alignments. Bioinformatics, 2006; 22:1536–1537.
18.
OjesinaA, ChaplinB, SankaléJ-Let al.Interplay of reverse transcriptase inhibitor therapy and Gag p6 diversity in HIV Type 1 subtype G and CRF02_AG. AIDS Res Hum Retroviruses, 2008; 24,9:1167–1174.
19.
LastereS, DalbanC, CollinGet al.Impact of insertions in the HIV-1 p6 PTAPP region on the virological response to amprenavir. Antiviral Ther, 2004; 9:221–227.
20.
VerheyenJ, LitauE, SingTet al.Compensatory mutations at the HIV cleavage sites p7/p1 and p1/p6-gag in therapy-naive and therapy-experienced patients. Antiviral Ther, 2006; 11,7:879–887.
21.
ShibataJ, SugiuraW, OdeHet al.Within-host co-evolution of gag P453L and protease D30N/N88D demonstrates virological advantage in a highly protease inhibitor-exposed HIV-1 case. Antiviral Res, 2011; 90,1:33–41.
