To study variability in reverse transcriptase (RT) and protease (PR) genes of HIV-1 isolated from recently infected patients identified between 1997 and 2003, sequences were obtained on the RT and PR genes of viruses harvested from plasma of 121 non-treated subjects who had undergone primary HIV infection. The degree of dissimilarity between the viruses studied and a reference HIV-1 subtype B strain (LAV-1) was calculated for each of RT and PR by counting all of the nucleotide substitutions that could be identified. Mutations associated with drug resistance were excluded from analysis. We observed a mean percentage of variation in the RT and PR genes of the viruses analysed of 0.42% between the years 1997–2003 (P<0.01). In PR, the mean variation was 0.71% (P<0.05), while that in RT was 0.3% (P<0.05). Increased diversity was also observed among nucleotides conferring amino-acid changes, although no significant differences in patterns of nucleotide substitutions were apparent over the period of analysis. In conclusion, variability in the RT and PR genes of viruses from recently infected patients has increased over time in a manner that is independent of variability attributable to HIV drug resistance.
BorrowPLewickiHHahnBHShawGM & OldstoneMB (1994) Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. Journal of Virology68: 6103–6110.
2.
BrennerBRoutyJPQuanYMoisiDOliveiraMTurnerDWainbergMA & co-investigators of the Quebec Primary Infection Study (2004) Persistence of multidrug-resistant HIV-1 in primary infection leading to superinfection. AIDS18: 1653–1660.
3.
BrennerBTurnerDOliveiraMMoisiDDetorioMCarobeneMMarlinkR-GSchapiroJ-MRogerM & WainbergMA (2003) A V106M mutation in HIV-1 clade C viruses exposed to efavirenz confers cross-resistance to non-nucleoside reverse transcriptase inhibitors. AIDS17: F1–5.
4.
HahnBHShawGMTaylorMERedfieldRRMarkhamPDSalahuddinSZWong-StaalFGalloRCParksES & ParksWP (1986) Genetic variation in HTLV-III/LAV over time in patients with AIDS or at risk for AIDS. Science232: 1548–1553.
5.
InouyePCherryEMaylaHZolla-PaznerS & WainbergMA (1998) Neutralizing antibodies directed against the V3 loop select for different escape variants in a virus with mutated reverse transcriptase (M184V) than in wild-type human immunodeficiency virus type 1. AIDS Research & Human Retroviruses14: 735–740.
6.
KoupRASafritJTCaoYAndrewsCAMcLeodGBorkowskyWFarthingC & HoDD (1994) Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. Journal of Virology68: 4650–4655.
7.
LiWHTanimuraM & SharpPM (1988) Rates and dates of divergence between AIDS virus nucleotide sequences. Molecular Biology & Evolution5: 313–330.
8.
LoembaHBrennerBParniakMAMaayanSSpiraBMoisiDOliveiraMDetorioM & WainbergMA (2002) Genetic diversity of human immunodeficiency virus type 1 Ethiopian clade C reverse transcriptase (RT) and rapid development of resistance against nonnucleoside inhibitors of RT. Antimicrobial Agents & Chemotherapy46: 2087–2094.
9.
MooreCBJohnMJamesIRChristiansenFTWittCS & MallalSA (2002) Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level. Science296: 1439–1443.
10.
OggGSJinXBonhoefferSDunbarPRNowakMAMonardSSegalJPCaoYRowland-JonesSLCerundoloVHurleyAMarkowitzMHoDDNixonDF & McMichaelAJ (1998) Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science279: 2103–2106.
11.
PrestonBD & DoughertyJP (1996) Mechanisms of retroviral mutation. Trends in Microbiology4: 16–21.
12.
Quinones-MateuMWeberJRangelH & CharkabortyB (2001) HIV-1 fitness and antiretroviral drug resistance. AIDS Reviews3: 223–242.
13.
RezendeLFDrosopoulosWC & PrasadVR (1998) The influence of the 3TC resistance mutation M184I on the fidelity and error specificity of human immunodeficiency virus type 1 reverse transcriptase. Nucleic Acids Research26: 3066–3072.
14.
RobertsJBebenekK & KunkelT (1998) The accuracy of reverse transcriptase from HIV-1. Science242: 1171–1173.
15.
SalomonHWainbergMABrennerBQuanYRouleauDCotePLeBlancRLefebvreESpiraBTsoukasCSekalyRPConwayBMayersD & RoutyJP (2000) Prevalence of HIV-1 resistant to antiretroviral drugs in 81 individuals newly infected by sexual contact or injecting drug use. Investigators of the Quebec Primary Infection Study. AIDS14: F17–23.
16.
SamriAHaasGDuntzeJBouleyJMCalvezVKatlamaC & AutranB (2000) Immunogenicity of mutations induced by nucleoside reverse transcriptase inhibitors for human immunodeficiency virus type 1-specific cytotoxic T cells. Journal of Virology74: 9306–9312.
17.
SchmittMHarrerEGoldwichABauerleMGraednerIKaldenJR & HarrerT (2000) Specific recognition of lamivudine-resistant HIV-1 by cytotoxic T lymphocytes. AIDS4: 653–658.
18.
ShankarappaRMargolickJBGangeSJRodrigoAGUpchurchDFarzadeganHGuptaPRinaldoCRLearnGHHeXHuangXL & MullinsJI (1999) Consistent viral evolutionary changes associated with the progression of human immunodeficiency virus type 1 infection. Journal of Virology73: 10489–10502.
19.
ThompsonJDGibsonTJPlewniakFJeanmouginF & HiggingDG (1997) The Clustal X windows interface: Flexible strategies of multiple sequence alignment aided by qualify analysis tools. Nucleic Acids Research25: 4876–4882.
20.
TurnerDBrennerBMoisiDDetorioMCesaireRKurimuraKMoriHEssexMMaayanS & WainbergMA (2004) Nucleotide and amino acid polymorphisms at drug resistance sites in non-B subtype variants of human immunodeficiency virus type 1. Antimicrobial Agents & Chemotherapy48: 2993–2998.
21.
TurnerDBrennerBRoutyJ-PMoisiDRosbergerZRogerM & WainbergM-A (2004) Diminished representation of HIV-1 variants containing select drug resistance-conferring mutations in primary HIV-1 infection. Journal of Acquired Immune Deficiency Syndromes (in press).
