Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1997 Mar;71(3):1871–1879. doi: 10.1128/jvi.71.3.1871-1879.1997

Evolution of human immunodeficiency virus type 1 env sequence variation in patients with diverse rates of disease progression and T-cell function.

R A McDonald 1, D L Mayers 1, R C Chung 1, K F Wagner 1, S Ratto-Kim 1, D L Birx 1, N L Michael 1
PMCID: PMC191257  PMID: 9032317

Abstract

We examined the relationship between env sequence variation and disease progression in 10 human immunodeficiency virus type 1 (HIV-1)-seropositive subjects selected from a longitudinal cohort receiving zidovudine therapy. Five subjects were chosen for stable clinical status and CD4 counts (slow progressors), and five were selected for rapid clinical deterioration and CD4 count decline (rapid progressors). The slow progressors had significantly lower plasma viral RNA loads and greater lymphoproliferative responses to mitogens than the rapid progressors. DNA sequences representing the C1 through C3 regions of env were amplified from two peripheral blood mononuclear cell DNA samples from each subject separated by an average of 2.5 years. Molecular clones of these amplicons were then sequenced, and DNA sequence and deduced amino acid sequence distances were compared. Inter-time point sequence comparison showed a higher rate of sequence evolution for the rapid progressors in three of five matched pairs of rapid progressors and slow progressors and for the slow progressors in the remaining two subject pairs. However, intra-time point sequence comparisons showed that four of five slow progressors developed a more diverse quasispecies over time and one showed no change. In contrast, four of five rapid progressors showed no change in quasispecies diversity over time and one showed a significant decrease in diversity. The overall C1 through C3 region quasispecies diversity in the slow progressors at baseline was lower than that for the rapid progressors, but this difference was not significant at the follow-up time points. These diversity relationships were obscured if sequence analyses were limited to the 300-bp C2 to V3 region. Thus, HIV-1 quasispecies diversity increased over time in subjects with more functional immune systems.

Full Text

The Full Text of this article is available as a PDF (117.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahmad N., Baroudy B. M., Baker R. C., Chappey C. Genetic analysis of human immunodeficiency virus type 1 envelope V3 region isolates from mothers and infants after perinatal transmission. J Virol. 1995 Feb;69(2):1001–1012. doi: 10.1128/jvi.69.2.1001-1012.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cao Y., Qin L., Zhang L., Safrit J., Ho D. D. Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N Engl J Med. 1995 Jan 26;332(4):201–208. doi: 10.1056/NEJM199501263320401. [DOI] [PubMed] [Google Scholar]
  3. Coffin J. M. Genetic diversity and evolution of retroviruses. Curr Top Microbiol Immunol. 1992;176:143–164. doi: 10.1007/978-3-642-77011-1_10. [DOI] [PubMed] [Google Scholar]
  4. Coffin J. M. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science. 1995 Jan 27;267(5197):483–489. doi: 10.1126/science.7824947. [DOI] [PubMed] [Google Scholar]
  5. Delwart E. L., Sheppard H. W., Walker B. D., Goudsmit J., Mullins J. I. Human immunodeficiency virus type 1 evolution in vivo tracked by DNA heteroduplex mobility assays. J Virol. 1994 Oct;68(10):6672–6683. doi: 10.1128/jvi.68.10.6672-6683.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goodenow M., Huet T., Saurin W., Kwok S., Sninsky J., Wain-Hobson S. HIV-1 isolates are rapidly evolving quasispecies: evidence for viral mixtures and preferred nucleotide substitutions. J Acquir Immune Defic Syndr. 1989;2(4):344–352. [PubMed] [Google Scholar]
  7. Goudsmit J., Back N. K., Nara P. L. Genomic diversity and antigenic variation of HIV-1: links between pathogenesis, epidemiology and vaccine development. FASEB J. 1991 Jul;5(10):2427–2436. doi: 10.1096/fasebj.5.10.2065891. [DOI] [PubMed] [Google Scholar]
  8. Hahn B. H., Shaw G. M., Taylor M. E., Redfield R. R., Markham P. D., Salahuddin S. Z., Wong-Staal F., Gallo R. C., Parks E. S., Parks W. P. Genetic variation in HTLV-III/LAV over time in patients with AIDS or at risk for AIDS. Science. 1986 Jun 20;232(4757):1548–1553. doi: 10.1126/science.3012778. [DOI] [PubMed] [Google Scholar]
  9. Harrer E., Harrer T., Buchbinder S., Mann D. L., Feinberg M., Yilma T., Johnson R. P., Walker B. D. HIV-1-specific cytotoxic T lymphocyte response in healthy, long-term nonprogressing seropositive persons. AIDS Res Hum Retroviruses. 1994;10 (Suppl 2):S77–S78. [PubMed] [Google Scholar]
  10. Ho D. D., Neumann A. U., Perelson A. S., Chen W., Leonard J. M., Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995 Jan 12;373(6510):123–126. doi: 10.1038/373123a0. [DOI] [PubMed] [Google Scholar]
  11. Keet I. P., Krijnen P., Koot M., Lange J. M., Miedema F., Goudsmit J., Coutinho R. A. Predictors of rapid progression to AIDS in HIV-1 seroconverters. AIDS. 1993 Jan;7(1):51–57. doi: 10.1097/00002030-199301000-00008. [DOI] [PubMed] [Google Scholar]
  12. Lamers S. L., Sleasman J. W., She J. X., Barrie K. A., Pomeroy S. M., Barrett D. J., Goodenow M. M. Independent variation and positive selection in env V1 and V2 domains within maternal-infant strains of human immunodeficiency virus type 1 in vivo. J Virol. 1993 Jul;67(7):3951–3960. doi: 10.1128/jvi.67.7.3951-3960.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lamers S. L., Sleasman J. W., She J. X., Barrie K. A., Pomeroy S. M., Barrett D. J., Goodenow M. M. Persistence of multiple maternal genotypes of human immunodeficiency virus type I in infants infected by vertical transmission. J Clin Invest. 1994 Jan;93(1):380–390. doi: 10.1172/JCI116970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lukashov V. V., Kuiken C. L., Goudsmit J. Intrahost human immunodeficiency virus type 1 evolution is related to length of the immunocompetent period. J Virol. 1995 Nov;69(11):6911–6916. doi: 10.1128/jvi.69.11.6911-6916.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mayers D. L., Japour A. J., Arduino J. M., Hammer S. M., Reichman R., Wagner K. F., Chung R., Lane J., Crumpacker C. S., McLeod G. X. Dideoxynucleoside resistance emerges with prolonged zidovudine monotherapy. The RV43 Study Group. Antimicrob Agents Chemother. 1994 Feb;38(2):307–314. doi: 10.1128/aac.38.2.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McNearney T., Hornickova Z., Markham R., Birdwell A., Arens M., Saah A., Ratner L. Relationship of human immunodeficiency virus type 1 sequence heterogeneity to stage of disease. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10247–10251. doi: 10.1073/pnas.89.21.10247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Meyerhans A., Cheynier R., Albert J., Seth M., Kwok S., Sninsky J., Morfeldt-Månson L., Asjö B., Wain-Hobson S. Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations. Cell. 1989 Sep 8;58(5):901–910. doi: 10.1016/0092-8674(89)90942-2. [DOI] [PubMed] [Google Scholar]
  18. Michael N. L., Davis K. E., Loomis-Price L. D., VanCott T. C., Burke D. S., Redfield R. R., Birx D. L. V3 seroreactivity and sequence variation: tracking the emergence of V3 genotypic variation in HIV-1-infected patients. AIDS. 1996 Feb;10(2):121–129. doi: 10.1097/00002030-199602000-00001. [DOI] [PubMed] [Google Scholar]
  19. Michael N. L., Vahey M., Burke D. S., Redfield R. R. Viral DNA and mRNA expression correlate with the stage of human immunodeficiency virus (HIV) type 1 infection in humans: evidence for viral replication in all stages of HIV disease. J Virol. 1992 Jan;66(1):310–316. doi: 10.1128/jvi.66.1.310-316.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nei M., Gojobori T. Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol. 1986 Sep;3(5):418–426. doi: 10.1093/oxfordjournals.molbev.a040410. [DOI] [PubMed] [Google Scholar]
  21. Nowak M. A., Anderson R. M., McLean A. R., Wolfs T. F., Goudsmit J., May R. M. Antigenic diversity thresholds and the development of AIDS. Science. 1991 Nov 15;254(5034):963–969. doi: 10.1126/science.1683006. [DOI] [PubMed] [Google Scholar]
  22. Pang S., Shlesinger Y., Daar E. S., Moudgil T., Ho D. D., Chen I. S. Rapid generation of sequence variation during primary HIV-1 infection. AIDS. 1992 May;6(5):453–460. doi: 10.1097/00002030-199205000-00003. [DOI] [PubMed] [Google Scholar]
  23. Pantaleo G., Menzo S., Vaccarezza M., Graziosi C., Cohen O. J., Demarest J. F., Montefiori D., Orenstein J. M., Fox C., Schrager L. K. Studies in subjects with long-term nonprogressive human immunodeficiency virus infection. N Engl J Med. 1995 Jan 26;332(4):209–216. doi: 10.1056/NEJM199501263320402. [DOI] [PubMed] [Google Scholar]
  24. Perelson A. S., Neumann A. U., Markowitz M., Leonard J. M., Ho D. D. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science. 1996 Mar 15;271(5255):1582–1586. doi: 10.1126/science.271.5255.1582. [DOI] [PubMed] [Google Scholar]
  25. Ratner L., Haseltine W., Patarca R., Livak K. J., Starcich B., Josephs S. F., Doran E. R., Rafalski J. A., Whitehorn E. A., Baumeister K. Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature. 1985 Jan 24;313(6000):277–284. doi: 10.1038/313277a0. [DOI] [PubMed] [Google Scholar]
  26. Rinaldo C., Huang X. L., Fan Z. F., Ding M., Beltz L., Logar A., Panicali D., Mazzara G., Liebmann J., Cottrill M. High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1-infected long-term nonprogressors. J Virol. 1995 Sep;69(9):5838–5842. doi: 10.1128/jvi.69.9.5838-5842.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Roos M. T., Miedema F., Koot M., Tersmette M., Schaasberg W. P., Coutinho R. A., Schellekens P. T. T cell function in vitro is an independent progression marker for AIDS in human immunodeficiency virus-infected asymptomatic subjects. J Infect Dis. 1995 Mar;171(3):531–536. doi: 10.1093/infdis/171.3.531. [DOI] [PubMed] [Google Scholar]
  28. Schwartz D., Sharma U., Busch M., Weinhold K., Matthews T., Lieberman J., Birx D., Farzedagen H., Margolick J., Quinn T. Absence of recoverable infectious virus and unique immune responses in an asymptomatic HIV+ long-term survivor. AIDS Res Hum Retroviruses. 1994 Dec;10(12):1703–1711. doi: 10.1089/aid.1994.10.1703. [DOI] [PubMed] [Google Scholar]
  29. Sheppard H. W., Ascher M. S., McRae B., Anderson R. E., Lang W., Allain J. P. The initial immune response to HIV and immune system activation determine the outcome of HIV disease. J Acquir Immune Defic Syndr. 1991;4(7):704–712. [PubMed] [Google Scholar]
  30. Simmonds P., Zhang L. Q., McOmish F., Balfe P., Ludlam C. A., Brown A. J. Discontinuous sequence change of human immunodeficiency virus (HIV) type 1 env sequences in plasma viral and lymphocyte-associated proviral populations in vivo: implications for models of HIV pathogenesis. J Virol. 1991 Nov;65(11):6266–6276. doi: 10.1128/jvi.65.11.6266-6276.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Smith S. W., Overbeek R., Woese C. R., Gilbert W., Gillevet P. M. The genetic data environment an expandable GUI for multiple sequence analysis. Comput Appl Biosci. 1994 Dec;10(6):671–675. doi: 10.1093/bioinformatics/10.6.671. [DOI] [PubMed] [Google Scholar]
  32. Starcich B. R., Hahn B. H., Shaw G. M., McNeely P. D., Modrow S., Wolf H., Parks E. S., Parks W. P., Josephs S. F., Gallo R. C. Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS. Cell. 1986 Jun 6;45(5):637–648. doi: 10.1016/0092-8674(86)90778-6. [DOI] [PubMed] [Google Scholar]
  33. Wain-Hobson S. Viral burden in AIDS. Nature. 1993 Nov 4;366(6450):22–22. doi: 10.1038/366022b0. [DOI] [PubMed] [Google Scholar]
  34. Wei X., Ghosh S. K., Taylor M. E., Johnson V. A., Emini E. A., Deutsch P., Lifson J. D., Bonhoeffer S., Nowak M. A., Hahn B. H. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 1995 Jan 12;373(6510):117–122. doi: 10.1038/373117a0. [DOI] [PubMed] [Google Scholar]
  35. Wolinsky S. M., Korber B. T., Neumann A. U., Daniels M., Kunstman K. J., Whetsell A. J., Furtado M. R., Cao Y., Ho D. D., Safrit J. T. Adaptive evolution of human immunodeficiency virus-type 1 during the natural course of infection. Science. 1996 Apr 26;272(5261):537–542. doi: 10.1126/science.272.5261.537. [DOI] [PubMed] [Google Scholar]
  36. Wolinsky S. M., Wike C. M., Korber B. T., Hutto C., Parks W. P., Rosenblum L. L., Kunstman K. J., Furtado M. R., Muñoz J. L. Selective transmission of human immunodeficiency virus type-1 variants from mothers to infants. Science. 1992 Feb 28;255(5048):1134–1137. doi: 10.1126/science.1546316. [DOI] [PubMed] [Google Scholar]
  37. Zhu T., Mo H., Wang N., Nam D. S., Cao Y., Koup R. A., Ho D. D. Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science. 1993 Aug 27;261(5125):1179–1181. doi: 10.1126/science.8356453. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES