1887

Abstract

The rapid spread of human immunodeficiency virus type 1 (HIV-1) in humans has been accompanied by continuous extensive genetic diversification of the virus. The aim of this study was to investigate the impact of HIV-1 diversification on HIV-1 replication capacity (RC) and mutational robustness. Thirty-three HIV-1 protease sequences were amplified from three groups of viruses: two naïve sample groups isolated 15 years apart plus a third group of protease inhibitor-(PI) resistant samples. The amplified proteases were recombined with an HXB2 infectious clone and RC was determined in MT-4 cells. RC was also measured in these three groups after random mutagenesis using error-prone PCR. No significant RC differences were observed between recombinant viruses from either early or recent naïve isolates ( = 0.5729), even though the proteases from the recent isolates had significantly lower sequence conservation scores compared with a subtype B ancestral sequence (<0.0001). Randomly mutated recombinant viruses from the three groups exhibited significantly lower RC values than the corresponding wild-type viruses (<0.0001). There was no significant difference regarding viral infectivity reduction between viruses carrying randomly mutated naïve proteases from early or recent sample isolates ( = 0.8035). Interestingly, a significantly greater loss of RC was observed in the PI-resistant protease group ( = 0.0400). These results demonstrate that protease sequence diversification has not affected HIV-1 RC or protease robustness and indicate that proteases carrying PI resistance substitutions are less robust than naïve proteases.

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2012-12-01
2020-10-31
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References

  1. Alizon S., von Wyl V., Stadler T., Kouyos R. D., Yerly S., Hirschel B., Böni J., Shah C., Klimkait T. other authors 2010; Phylogenetic approach reveals that virus genotype largely determines HIV set-point viral load. PLoS Pathog 6:e1001123 [CrossRef][PubMed]
    [Google Scholar]
  2. Ariën K. K., Troyer R. M., Gali Y., Colebunders R. L., Arts E. J., Vanham G. 2005; Replicative fitness of historical and recent HIV-1 isolates suggests HIV-1 attenuation over time. AIDS 19:1555–1564 [CrossRef][PubMed]
    [Google Scholar]
  3. Ariën K. K., Vanham G., Arts E. J. 2007; Is HIV-1 evolving to a less virulent form in humans?. Nat Rev Microbiol 5:141–151 [CrossRef][PubMed]
    [Google Scholar]
  4. Betancor G., Puertas M. C., Nevot M., Garriga C., Martínez M. A., Martinez-Picado J., Menéndez-Arias L. 2010; Mechanisms involved in the selection of HIV-1 reverse transcriptase thumb subdomain polymorphisms associated with nucleoside analogue therapy failure. Antimicrob Agents Chemother 54:4799–4811 [CrossRef][PubMed]
    [Google Scholar]
  5. Chopera D. R., Mlotshwa M., Woodman Z., Mlisana K., de Assis Rosa D., Martin D. P., Abdool Karim S., Gray C. M., Williamson C. CAPRISA 002 Study Team 2011; Virological and immunological factors associated with HIV-1 differential disease progression in HLA-B 58:01-positive individuals. J Virol 85:7070–7080 [CrossRef][PubMed]
    [Google Scholar]
  6. Derdeyn C. A., Decker J. M., Bibollet-Ruche F., Mokili J. L., Muldoon M., Denham S. A., Heil M. L., Kasolo F., Musonda R. other authors 2004; Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission. Science 303:2019–2022 [CrossRef][PubMed]
    [Google Scholar]
  7. Dorrucci M., Phillips A. N., Longo B., Rezza G. Italian Seroconversion Study 2005; Changes over time in post-seroconversion CD4 cell counts in the Italian HIV-Seroconversion Study: 1985-2002. AIDS 19:331–335[PubMed]
    [Google Scholar]
  8. Dorrucci M., Rezza G., Porter K., Phillips A. Concerted Action on Seroconversion to AIDS and Death in Europe Collaboration 2007; Temporal trends in postseroconversion CD4 cell count and HIV load: the Concerted Action on Seroconversion to AIDS and Death in Europe Collaboration, 1985-2002. J Infect Dis 195:525–534 [CrossRef][PubMed]
    [Google Scholar]
  9. Draghi J. A., Parsons T. L., Wagner G. P., Plotkin J. B. 2010; Mutational robustness can facilitate adaptation. Nature 463:353–355 [CrossRef][PubMed]
    [Google Scholar]
  10. Fernàndez G., Clotet B., Martínez M. A. 2007; Fitness landscape of human immunodeficiency virus type 1 protease quasispecies. J Virol 81:2485–2496 [CrossRef][PubMed]
    [Google Scholar]
  11. Gali Y., Berkhout B., Vanham G., Bakker M., Back N. K., Ariën K. K. 2007; Survey of the temporal changes in HIV-1 replicative fitness in the Amsterdam Cohort. Virology 364:140–146 [CrossRef][PubMed]
    [Google Scholar]
  12. Hemelaar J. 2012; The origin and diversity of the HIV-1 pandemic. Trends Mol Med 18:182–192 [CrossRef][PubMed]
    [Google Scholar]
  13. Herbeck J. T., Gottlieb G. S., Li X., Hu Z., Detels R., Phair J., Rinaldo C., Jacobson L. P., Margolick J. B., Mullins J. I. 2008; Lack of evidence for changing virulence of HIV-1 in North America. PLoS ONE 3:e1525 [CrossRef][PubMed]
    [Google Scholar]
  14. Herbeck J. T., Müller V., Maust B. S., Ledergerber B., Torti C., Di Giambenedetto S., Gras L., Günthard H. F., Jacobson L. P. other authors 2012; Is the virulence of HIV changing? A meta-analysis of trends in prognostic markers of HIV disease progression and transmission. AIDS 26:193–205 [CrossRef][PubMed]
    [Google Scholar]
  15. Ibáñez A., Clotet B., Martínez M. A. 2000; Human immunodeficiency virus type 1 population bottleneck during indinavir therapy causes a genetic drift in the env quasispecies. J Gen Virol 81:85–95[PubMed]
    [Google Scholar]
  16. Kawashima Y., Pfafferott K., Frater J., Matthews P., Payne R., Addo M., Gatanaga H., Fujiwara M., Hachiya A. other authors 2009; Adaptation of HIV-1 to human leukocyte antigen class I. Nature 458:641–645 [CrossRef][PubMed]
    [Google Scholar]
  17. Kearney M., Maldarelli F., Shao W., Margolick J. B., Daar E. S., Mellors J. W., Rao V., Coffin J. M., Palmer S. 2009; Human immunodeficiency virus type 1 population genetics and adaptation in newly infected individuals. J Virol 83:2715–2727 [CrossRef][PubMed]
    [Google Scholar]
  18. Keele B. F., Giorgi E. E., Salazar-Gonzalez J. F., Decker J. M., Pham K. T., Salazar M. G., Sun C., Grayson T., Wang S. other authors 2008; Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A 105:7552–7557 [CrossRef][PubMed]
    [Google Scholar]
  19. Kisic M., Matamoros T., Nevot M., Mendieta J., Martinez-Picado J., Martínez M. A., Menéndez-Arias L. 2011; Thymidine analogue excision and discrimination modulated by mutational complexes including single amino acid deletions of Asp-67 or Thr-69 in HIV-1 reverse transcriptase. J Biol Chem 286:20615–20624 [CrossRef][PubMed]
    [Google Scholar]
  20. Korber B., Muldoon M., Theiler J., Gao F., Gupta R., Lapedes A., Hahn B. H., Wolinsky S., Bhattacharya T. 2000; Timing the ancestor of the HIV-1 pandemic strains. Science 288:1789–1796 [CrossRef][PubMed]
    [Google Scholar]
  21. Kosakovsky Pond S. L., Frost S. D. 2005; Not so different after all: a comparison of methods for detecting amino acid sites under selection. Mol Biol Evol 22:1208–1222 [CrossRef][PubMed]
    [Google Scholar]
  22. Leslie A. J., Pfafferott K. J., Chetty P., Draenert R., Addo M. M., Feeney M., Tang Y., Holmes E. C., Allen T. other authors 2004; HIV evolution: CTL escape mutation and reversion after transmission. Nat Med 10:282–289 [CrossRef][PubMed]
    [Google Scholar]
  23. Loeb D. D., Swanstrom R., Everitt L., Manchester M., Stamper S. E., Hutchison C. A. III 1989; Complete mutagenesis of the HIV-1 protease. Nature 340:397–400 [CrossRef][PubMed]
    [Google Scholar]
  24. Martinez-Picado J., Martínez M. A. 2008; HIV-1 reverse transcriptase inhibitor resistance mutations and fitness: a view from the clinic and ex vivo. Virus Res 134:104–123 [CrossRef][PubMed]
    [Google Scholar]
  25. Martinez-Picado J., Savara A. V., Sutton L., D’Aquila R. T. 1999; Replicative fitness of protease inhibitor-resistant mutants of human immunodeficiency virus type 1. J Virol 73:3744–3752[PubMed]
    [Google Scholar]
  26. Más A., López-Galíndez C., Cacho I., Gómez J., Martínez M. A. 2010; Unfinished stories on viral quasispecies and Darwinian views of evolution. J Mol Biol 397:865–877 [CrossRef][PubMed]
    [Google Scholar]
  27. Maschera B., Furfine E., Blair E. D. 1995; Analysis of resistance to human immunodeficiency virus type 1 protease inhibitors by using matched bacterial expression and proviral infection vectors. J Virol 69:5431–5436[PubMed]
    [Google Scholar]
  28. Miura T., Brockman M. A., Brumme Z. L., Brumme C. J., Pereyra F., Trocha A., Block B. L., Schneidewind A., Allen T. M. other authors 2009; HLA-associated alterations in replication capacity of chimeric NL4-3 viruses carrying gag-protease from elite controllers of human immunodeficiency virus type 1. J Virol 83:140–149 [CrossRef][PubMed]
    [Google Scholar]
  29. Muller H. J. 1964; The relation of recombination to mutational advance. Mutat Res 106:2–9[PubMed] [CrossRef]
    [Google Scholar]
  30. Müller V., Ledergerber B., Perrin L., Klimkait T., Furrer H., Telenti A., Bernasconi E., Vernazza P., Günthard H. F., Bonhoeffer S. Swiss HIV Cohort Study 2006; Stable virulence levels in the HIV epidemic of Switzerland over two decades. AIDS 20:889–894 [CrossRef][PubMed]
    [Google Scholar]
  31. Nevot M., Martrus G., Clotet B., Martínez M. A. 2011; RNA interference as a tool for exploring HIV-1 robustness. J Mol Biol 413:84–96 [CrossRef][PubMed]
    [Google Scholar]
  32. Nijhuis M., Schuurman R., de Jong D., Erickson J., Gustchina E., Albert J., Schipper P., Gulnik S., Boucher C. A. 1999; Increased fitness of drug resistant HIV-1 protease as a result of acquisition of compensatory mutations during suboptimal therapy. AIDS 13:2349–2359 [CrossRef][PubMed]
    [Google Scholar]
  33. Parera M., Ibañez A., Clotet B., Martinez M. A. 2004; Lack of evidence for protease evolution in HIV-1-infected patients after 2 years of successful highly active antiretroviral therapy. J Infect Dis 189:1444–1451 [CrossRef][PubMed]
    [Google Scholar]
  34. Parera M., Fernàndez G., Clotet B., Martínez M. A. 2007; HIV-1 protease catalytic efficiency effects caused by random single amino acid substitutions. Mol Biol Evol 24:382–387 [CrossRef][PubMed]
    [Google Scholar]
  35. Rolland M., Brander C., Nickle D. C., Herbeck J. T., Gottlieb G. S., Campbell M. S., Maust B. S., Mullins J. I. 2007; HIV-1 over time: fitness loss or robustness gain?. Nat Rev Microbiol 5:1–2 [CrossRef][PubMed]
    [Google Scholar]
  36. Sharp P. M., Hahn B. H. 2011; Origins of HIV and the AIDS pandemic. Cold Spring Harb Perspect Med 1:a006841[PubMed] [CrossRef]
    [Google Scholar]
  37. Sinicco A., Fora R., Raiteri R., Sciandra M., Bechis G., Calvo M. M., Gioannini P. 1997; Is the clinical course of HIV-1 changing? Cohort study. BMJ 314:1232–1237 [CrossRef][PubMed]
    [Google Scholar]
  38. Stoddart C. A., Liegler T. J., Mammano F., Linquist-Stepps V. D., Hayden M. S., Deeks S. G., Grant R. M., Clavel F., McCune J. M. 2001; Impaired replication of protease inhibitor-resistant HIV-1 in human thymus. Nat Med 7:712–718 [CrossRef][PubMed]
    [Google Scholar]
  39. Tamura K., Dudley J., Nei M., Kumar S. 2007; mega4: Molecular Evolutionary Genetics Analysis (mega) software version 4.0. Mol Biol Evol 24:1596–1599 [CrossRef][PubMed]
    [Google Scholar]
  40. Troude P., Chaix M. L., Tran L., Deveau C., Seng R., Delfraissy J. F., Rouzioux C., Goujard C., Meyer L. ANRS Primo cohort 2009; No evidence of a change in HIV-1 virulence since 1996 in France. AIDS 23:1261–1267 [CrossRef][PubMed]
    [Google Scholar]
  41. Troyer R. M., McNevin J., Liu Y., Zhang S. C., Krizan R. W., Abraha A., Tebit D. M., Zhao H., Avila S. other authors 2009; Variable fitness impact of HIV-1 escape mutations to cytotoxic T lymphocyte (CTL) response. PLoS Pathog 5:e1000365 [CrossRef][PubMed]
    [Google Scholar]
  42. van Manen D., Gras L., Boeser-Nunnink B. D., van Sighem A. I., Maurer I., Mangas Ruiz M. M., Harskamp A. M., Steingrover R., Prins J. M. other authors 2011; Rising HIV-1 viral load set point at a population level coincides with a fading impact of host genetic factors on HIV-1 control. AIDS 25:2217–2226 [CrossRef][PubMed]
    [Google Scholar]
  43. van Nimwegen E. 2006; Epidemiology. Influenza escapes immunity along neutral networks. Science 314:1884–1886 [CrossRef][PubMed]
    [Google Scholar]
  44. Vanhems P., Lambert J., Guerra M., Hirschel B., Allard R. 1999; Association between the rate of CD4+ T cell decrease and the year of human immunodeficiency virus (HIV) type 1 seroconversion among persons enrolled in the Swiss HIV cohort study. J Infect Dis 180:1803–1808 [CrossRef][PubMed]
    [Google Scholar]
  45. Vermund S. H., Leigh-Brown A. J. 2012; The HIV Epidemic: high-income countries. Cold Spring Harb Perspect Med 2:a007195[PubMed] [CrossRef]
    [Google Scholar]
  46. Walker B., McMichael A. 2012; The T-cell response to HIV. Cold Spring Harb Perspect Med (in press). doi:10.1101/cshperspect.a007054 [CrossRef]
    [Google Scholar]
  47. Wild G., Gardner A., West S. A. 2009; Adaptation and the evolution of parasite virulence in a connected world. Nature 459:983–986 [CrossRef][PubMed]
    [Google Scholar]
  48. Yuste E., Sánchez-Palomino S., Casado C., Domingo E., López-Galíndez C. 1999; Drastic fitness loss in human immunodeficiency virus type 1 upon serial bottleneck events. J Virol 73:2745–2751[PubMed]
    [Google Scholar]
  49. Yuste E., López-Galíndez C., Domingo E. 2000; Unusual distribution of mutations associated with serial bottleneck passages of human immunodeficiency virus type 1. J Virol 74:9546–9552 [CrossRef][PubMed]
    [Google Scholar]
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