1887

Journal of General Virology header logo

Volume 86, Issue 10

Selection of human immunodeficiency virus type 1 R5 variants with augmented replicative capacity and reduced sensitivity to entry inhibitors during severe immunodeficiency Free

Abstract

Early in human immunodeficiency virus 1 (HIV-1) infection CCR5-using (R5) viruses predominate. With disease progression, approximately 50 % of infected individuals develop viruses able to use CXCR4. In the present work, the evolution of the biological properties of HIV-1 was studied in patients who retain viruses with an R5 phenotype despite AIDS onset. A panel of primary R5 HIV-1 isolates sequentially obtained at an asymptomatic stage and after AIDS diagnosis was examined. The viruses were selected based on our previous observation that R5 variants with reduced sensitivity to RANTES inhibition may appear during disease progression. Biological properties of the early and late R5 viruses, including infectivity, replicative capacity, impact of cationic polymer and sensitivity to inhibition by the entry inhibitors T-20 and TAK-779, were evaluated. R5 viruses isolated after AIDS onset displayed elevated replicative capacity and infectivity, and did not benefit from cationic polymer assistance during infection. Late R5 isolates also exhibited reduced sensitivity to inhibition by T-20 and TAK-779, even though the included patients were naïve to treatment with entry inhibitors and the isolates had not acquired mutations within the gp41 HR1 region. In addition, CD4 T-cell counts at the time of R5 virus isolation correlated with infectivity, replicative capacity and sensitivity to inhibition by entry inhibitors. The results indicate that R5 HIV-1 variants with augmented replicative capacity and reduced sensitivity to entry inhibitors may be selected for during severe immunodeficiency. At a time when the clinical use of entry inhibitors is increasing, this observation could be of importance in the optimal design of such treatments.

  • Received:
  • Accepted:
  • Published Online:
SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81111-0
2005-10-01
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/10/2859.html?itemId=/content/journal/jgv/10.1099/vir.0.81111-0&mimeType=html&fmt=ahah

References

  1. Albert J., Abrahamsson B., Nagy K., Aurelius E., Gaines H., Nystrom G., Fenyo E. M. 1990; Rapid development of isolate-specific neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera. AIDS 4:107–112 [CrossRef]
     [Google Scholar]
  2. Baba M., Nishimura O., Kanzaki N. 9 other authors 1999; A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity. Proc Natl Acad Sci U S A 96:5698–5703 [CrossRef]
     [Google Scholar]
  3. Bachrach E., Dreja H., Lin Y. L., Mettling C., Pinet V., Corbeau P., Piechaczyk M. 2005; Effects of virion surface gp120 density on infection by HIV-1 and viral production by infected cells. Virology 332:418–429 [CrossRef]
     [Google Scholar]
  4. Berger E. A., Murphy P. M., Farber J. M. 1999; Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol 17:657–700 [CrossRef]
     [Google Scholar]
  5. Bjorndal A., Deng H., Jansson M. 7 other authors 1997; Coreceptor usage of primary human immunodeficiency virus type 1 isolates varies according to biological phenotype. J Virol 71:7478–7487
     [Google Scholar]
  6. Blaak H., van't Wout A. B., Brouwer M., Hooibrink B., Hovenkamp E., Schuitemaker H. 2000; In vivo HIV-1 infection of CD45RA+CD4+ T cells is established primarily by syncytium-inducing variants and correlates with the rate of CD4+ T cell decline. Proc Natl Acad Sci U S A 97:1269–1274 [CrossRef]
     [Google Scholar]
  7. Cheng-Mayer C., Liu R., Landau N. R., Stamatatos L. 1997; Macrophage tropism of human immunodeficiency virus type 1 and utilization of the CC-CKR5 coreceptor. J Virol 71:1657–1661
     [Google Scholar]
  8. Clerici M., Balotta C., Meroni L. 8 other authors 1996; Type 1 cytokine production and low prevalence of viral isolation correlate with long-term nonprogression in HIV infection. AIDS Res Hum Retroviruses 12:1053–1061 [CrossRef]
     [Google Scholar]
  9. Cocchi F., DeVico A. L., Garzino-Demo A., Arya S. K., Gallo R. C., Lusso P. 1995; Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science 270:1811–1815 [CrossRef]
     [Google Scholar]
  10. Connor R. I., Sheridan K. E., Ceradini D., Choe S., Landau N. R. 1997; Change in coreceptor use correlates with disease progression in HIV-1-infected individuals. J Exp Med 185:621–628 [CrossRef]
     [Google Scholar]
  11. Corrigan G. E., Al-Khalili L., Malmsten A., Thorstensson R., Fenyo E. M., Kallander C. F., Gronowitz J. S. 1998; Differences in reverse transcriptase activity versus p24 antigen detection in cell culture, when comparing a homogeneous group of HIV type 1 subtype B viruses with a heterogeneous group of divergent strains. AIDS Res Hum Retroviruses 14:347–352 [CrossRef]
     [Google Scholar]
  12. Davis H. E., Morgan J. R., Yarmush M. L. 2002; Polybrene increases retrovirus gene transfer efficiency by enhancing receptor-independent virus adsorption on target cell membranes. Biophys Chem 97:159–172 [CrossRef]
     [Google Scholar]
  13. Deng H., Liu R., Ellmeier W. 12 other authors 1996; Identification of a major co-receptor for primary isolates of HIV-1. Nature 381:661–666 [CrossRef]
     [Google Scholar]
  14. de Roda Husman A. M., van Rij R. P., Blaak H., Broersen S., Schuitemaker H. 1999; Adaptation to promiscuous usage of chemokine receptors is not a prerequisite for human immunodeficiency virus type 1 disease progression. J Infect Dis 180:1106–1115 [CrossRef]
     [Google Scholar]
  15. Dragic T., Litwin V., Allaway G. P. 8 other authors 1996; HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 381:667–673 [CrossRef]
     [Google Scholar]
  16. Dragic T., Trkola A., Thompson D. A. 8 other authors 2000; A binding pocket for a small molecule inhibitor of HIV-1 entry within the transmembrane helices of CCR5. Proc Natl Acad Sci U S A 97:5639–5644 [CrossRef]
     [Google Scholar]
  17. Feng Y., Broder C. C., Kennedy P. E., Berger E. A. 1996; HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272:872–877 [CrossRef]
     [Google Scholar]
  18. Fenyö E. M. 2001; The role of virus biological phenotype in human immunodeficiency virus pathogenesis. AIDS Rev 3:157–168
     [Google Scholar]
  19. Gorry P. R., Taylor J., Holm G. H. 10 other authors 2002; Increased CCR5 affinity and reduced CCR5/CD4 dependence of a neurovirulent primary human immunodeficiency virus type 1 isolate. J Virol 76:6277–6292 [CrossRef]
     [Google Scholar]
  20. Greenberg M., Cammack N., Salgo M., Smiley L. 2004; HIV fusion and its inhibition in antiretroviral therapy. Rev Med Virol 14:321–337 [CrossRef]
     [Google Scholar]
  21. Harouse J. M., Buckner C., Gettie A., Fuller R., Bohm R., Blanchard J., Cheng-Mayer C. 2003; CD8+ T cell-mediated CXC chemokine receptor 4-simian/human immunodeficiency virus suppression in dually infected rhesus macaques. Proc Natl Acad Sci U S A 100:10977–10982 [CrossRef]
     [Google Scholar]
  22. Jansson M., Popovic M., Karlsson A., Cocchi F., Rossi P., Albert J., Wigzell H. 1996; Sensitivity to inhibition by beta-chemokines correlates with biological phenotypes of primary HIV-1 isolates. Proc Natl Acad Sci U S A 93:15382–15387 [CrossRef]
     [Google Scholar]
  23. Jansson M., Backstrom E., Bjorndal A., Holmberg V., Rossi P., Fenyo E. M., Popovic M., Albert J., Wigzell H. 1999; Coreceptor usage and RANTES sensitivity of non-syncytium-inducing HIV-1 isolates obtained from patients with AIDS. J Hum Virol 2:325–338
     [Google Scholar]
  24. Karlsson A., Bratt G., Von Krogh G., Morfeldt-Manson L., Bottiger B., Sandstrom E. 1991; A prospective study of 115 initially asymptomatic HIV infected gay men in Stockholm, Sweden. Scand J Infect Dis 23:431–441 [CrossRef]
     [Google Scholar]
  25. Karlsson A., Parsmyr K., Aperia K., Sandstrom E., Fenyo E. M., Albert J. 1994; MT-2 cell tropism of human immunodeficiency virus type 1 isolates as a marker for response to treatment and development of drug resistance. J Infect Dis 170:1367–1375 [CrossRef]
     [Google Scholar]
  26. Karlsson I., Antonsson L., Shi Y. 7 other authors 2004; Coevolution of RANTES sensitivity and mode of CCR5 receptor use by human immunodeficiency virus type 1 of the R5 phenotype. J Virol 78:11807–11815 [CrossRef]
     [Google Scholar]
  27. Kilby J. M., Hopkins S., Venetta T. M. 12 other authors 1998; Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat Med 4:1302–1307 [CrossRef]
     [Google Scholar]
  28. Koning F. A., Kwa D., Boeser-Nunnink B., Dekker J., Vingerhoed J., Hiemstra H., Schuitemaker H. 2003; Decreasing sensitivity to RANTES (regulated on activation, normally T cell-expressed and -secreted) neutralization of CC chemokine receptor 5-using, non-syncytium-inducing virus variants in the course of human immunodeficiency virus type 1 infection. J Infect Dis 188:864–872 [CrossRef]
     [Google Scholar]
  29. Koot M., Vos A. H., Keet R. P., de Goede R. E., Dercksen M. W., Terpstra F. G., Coutinho R. A., Miedema F., Tersmette M. 1992; HIV-1 biological phenotype in long-term infected individuals evaluated with an MT-2 cocultivation assay. AIDS 6:49–54 [CrossRef]
     [Google Scholar]
  30. LaBranche C. C., Galasso G., Moore J. P., Bolognesi D. P., Hirsch M. S., Hammer S. M. 2001; HIV fusion and its inhibition. Antiviral Res 50:95–115 [CrossRef]
     [Google Scholar]
  31. Labrosse B., Labernardiere J. L., Dam E., Trouplin V., Skrabal K., Clavel F., Mammano F. 2003; Baseline susceptibility of primary human immunodeficiency virus type 1 to entry inhibitors. J Virol 77:1610–1613 [CrossRef]
     [Google Scholar]
  32. Llano A., Barretina J., Gutierrez A., Blanco J., Cabrera C., Clotet B., Este J. A. 2001; Interleukin-7 in plasma correlates with CD4 T-cell depletion and may be associated with emergence of syncytium-inducing variants in human immunodeficiency virus type 1-positive individuals. J Virol 75:10319–10325 [CrossRef]
     [Google Scholar]
  33. Malmsten A., Shao X. W., Aperia K., Corrigan G. E., Sandstrom E., Kallander C. F., Leitner T., Gronowitz J. S. 2003; HIV-1 viral load determination based on reverse transcriptase activity recovered from human plasma. J Med Virol 71:347–359 [CrossRef]
     [Google Scholar]
  34. Mansky L. M. 2002; HIV mutagenesis and the evolution of antiretroviral drug resistance. Drug Resist Updates 5:219–223 [CrossRef]
     [Google Scholar]
  35. Mansky L. M., Pearl D. K., Gajary L. C. 2002; Combination of drugs and drug-resistant reverse transcriptase results in a multiplicative increase of human immunodeficiency virus type 1 mutant frequencies. J Virol 76:9253–9259 [CrossRef]
     [Google Scholar]
  36. Marozsan A. J., Fraundorf E., Abraha A., Baird H., Moore D., Troyer R., Nankja I., Arts E. J. 2004; Relationships between infectious titer, capsid protein levels, and reverse transcriptase activities of diverse human immunodeficiency virus type 1 isolates. J Virol 78:11130–11141 [CrossRef]
     [Google Scholar]
  37. Moore J. P., Doms R. W. 2003; The entry of entry inhibitors: a fusion of science and medicine. Proc Natl Acad Sci U S A 100:10598–10602 [CrossRef]
     [Google Scholar]
  38. Patterson B. K., Czerniewski M., Andersson J., Sullivan Y., Su F., Jiyamapa D., Burki Z., Landay A. 1999; Regulation of CCR5 and CXCR4 expression by type 1 and type 2 cytokines: CCR5 expression is downregulated by IL-10 in CD4-positive lymphocytes. Clin Immunol 91:254–262 [CrossRef]
     [Google Scholar]
  39. Reeves J. D., Gallo S. A., Ahmad N. 9 other authors 2002; Sensitivity of HIV-1 to entry inhibitors correlates with envelope/coreceptor affinity, receptor density, and fusion kinetics. Proc Natl Acad Sci U S A 99:16249–16254 [CrossRef]
     [Google Scholar]
  40. Richman D. D., Wrin T., Little S. J., Petropoulos C. J. 2003; Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proc Natl Acad Sci U S A 100:4144–4149 [CrossRef]
     [Google Scholar]
  41. Rimsky L. T., Shugars D. C., Matthews T. J. 1998; Determinants of human immunodeficiency virus type 1 resistance to gp41-derived inhibitory peptides. J Virol 72:986–993
     [Google Scholar]
  42. Samson M., Libert F., Doranz B. J. 19 other authors 1996; Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382:722–725 [CrossRef]
     [Google Scholar]
  43. Shi Y., Albert J., Francis G., Holmes H., Fenyo E. M. 2002; A new cell line-based neutralization assay for primary HIV type 1 isolates. AIDS Res Hum Retroviruses 18:957–967 [CrossRef]
     [Google Scholar]
  44. Takashima K., Miyake H., Furuta R. A., Fujisawa J. I., Iizawa Y., Kanzaki N., Shiraishi M., Okonogi K., Baba M. 2001; Inhibitory effects of small-molecule CCR5 antagonists on human immunodeficiency virus type 1 envelope-mediated membrane fusion and viral replication. Antimicrob Agents Chemother 45:3538–3543 [CrossRef]
     [Google Scholar]
  45. Trkola A., Kuhmann S. E., Strizki J. M. 14 other authors 2002; HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use. Proc Natl Acad Sci U S A 99:395–400 [CrossRef]
     [Google Scholar]
  46. Ullum H., Cozzi Lepri A., Victor J., Aladdin H., Phillips A. N., Gerstoft J., Skinhoj P., Pedersen B. K. 1998; Production of beta-chemokines in human immunodeficiency virus (HIV) infection: evidence that high levels of macrophage inflammatory protein-1beta are associated with a decreased risk of HIV disease progression. J Infect Dis 177:331–336 [CrossRef]
     [Google Scholar]
  47. Valentin A., Lu W., Rosati M., Schneider R., Albert J., Karlsson A., Pavlakis G. N. 1998; Dual effect of interleukin 4 on HIV-1 expression: implications for viral phenotypic switch and disease progression. Proc Natl Acad Sci U S A 95:8886–8891 [CrossRef]
     [Google Scholar]
  48. van Rij R. P., Blaak H., Visser J. A., Brouwer M., Rientsma R., Broersen S., de Roda Husman A. M., Schuitemaker H. 2000; Differential coreceptor expression allows for independent evolution of non-syncytium-inducing and syncytium-inducing HIV-1. J Clin Invest 106:1569 [CrossRef]
     [Google Scholar]
  49. van't Wout A. B., Kootstra N. A., Mulder-Kampinga G. A. 7 other authors 1994; Macrophage-tropic variants initiate human immunodeficiency virus type 1 infection after sexual, parenteral, and vertical transmission. J Clin Invest 94:2060–2067 [CrossRef]
     [Google Scholar]
  50. Wei X., Decker J. M., Liu H. 7 other authors 2002; Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob Agents Chemother 46:1896–1905 [CrossRef]
     [Google Scholar]
  51. Wild C. T., Shugars D. C., Greenwell T. K., McDanal C. B., Matthews T. J. 1994; Peptides corresponding to a predictive alpha-helical domain of human immunodeficiency virus type 1 gp41 are potent inhibitors of virus infection. Proc Natl Acad Sci U S A 91:9770–9774 [CrossRef]
     [Google Scholar]
  52. Yuste E., Reeves J. D., Doms R. W., Desrosiers R. C. 2004; Modulation of Env content in virions of simian immunodeficiency virus: correlation with cell surface expression and virion infectivity. J Virol 78:6775–6785 [CrossRef]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81111-0
Loading
Selection of human immunodeficiency virus type 1 R5 variants with augmented replicative capacity and reduced sensitivity to entry inhibitors during severe immunodeficiency
J. Gen. Virol. 86, 2859 (2005); https://doi.org/10.1099/vir.0.81111-0
/content/journal/jgv/10.1099/vir.0.81111-0
/content/journal/jgv/10.1099/vir.0.81111-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error