1887

Abstract

Human immunodeficiency virus type 1 (HIV-1) isolates can be distinguished by their chemokine coreceptor usage. Non-syncytium-inducing (NSI), macrophage-tropic viruses utilize CCR5 and are called R5 viruses; syncytium-inducing (SI) isolates use CXCR4 and are known as X4 viruses. R5 and X4 HIV isolates are both transmitted but, in most cases, R5 viruses predominate in the blood prior to the development of AIDS-related pathogenesis. The reason for the selective growth of the R5 strain is not known, but could reflect a replication advantage of R5 viruses over X4 viruses in CD4 cells. To explore this possibility, eight phenotypically distinct viruses were used to infect CD4 cells and cellular proliferation and activation were evaluated. In unstimulated CD4 cells, R5 virus isolates increased the level of cell activation compared with X4 virus isolates and uninfected control cells. In CD4 cells that were stimulated with interleukin 2, both R5 and X4 viruses were found to decrease the level of cell proliferation and reduce the majority of the activation markers studied when compared with uninfected control CD4 cells from the same donors. However, although equal amounts of CD4 cells were infected, R5 virus-infected CD4 cells showed a two- to fourfold increase in cellular proliferation over X4 viruses, as measured by [H]thymidine incorporation (=0·001) and nuclear expression of Ki67 (=0·001). In addition, a larger proportion of CD4 T cells infected with R5 viruses had significantly higher levels of activation-marker expression (e.g. CD25, CD71 and HLA-DR) than CD4 T lymphocytes infected with X4 viruses (<0·02). Taken together, these results indicate that CD4 cells infected with R5 virus isolates may have a selective advantage over X4 virus-infected CD4 T cells for survival and, hence, virus spread.

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2005-04-01
2024-03-30
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References

  1. Annunziato F., Galli G., Nappi F., Cosmi L., Manetti R., Maggi E., Ensoli B., Romagnani S. 2000; Limited expression of R5-tropic HIV-1 in CCR5-positive type 1-polarized T cells explained by their ability to produce RANTES. MIP-1 α and MIP1β . Blood 95:1167–1174
    [Google Scholar]
  2. Berger E. A. 1997; HIV entry and tropism: the chemokine receptor connection. AIDS 11 (Suppl. A):S3–S16
    [Google Scholar]
  3. Berkowitz R. D., Alexander S., Bare C. 8 other authors 1998; CCR5- and CXCR4-utilizing strains of human immunodeficiency virus type 1 exhibit differential tropism and pathogenesis in vivo. J Virol 72:10108–10117
    [Google Scholar]
  4. 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]
  5. Castro B. A., Weiss C. D., Wiviott L. D., Levy J. A. 1988; Optimal conditions for recovery of the human immunodeficiency virus from peripheral blood mononuclear cells. J Clin Microbiol 26:2371–2376
    [Google Scholar]
  6. Cheng-Mayer C., Levy J. A. 1988; Distinct biological and serological properties of human immunodeficiency viruses from the brain. Ann Neurol 23:Suppl.S58–S61 [CrossRef]
    [Google Scholar]
  7. Cheng-Mayer C., Seto D., Tateno M., Levy J. A. 1988; Biologic features of HIV-1 that correlate with virulence in the host. Science 240:80–82 [CrossRef]
    [Google Scholar]
  8. Cheng-Mayer C., Quiroga M., Tung J. W., Dina D., Levy J. A. 1990; Viral determinants of human immunodeficiency virus type 1 T-cell or macrophage tropism, cytopathogenicity, and CD4 antigen modulation. J Virol 64:4390–4398
    [Google Scholar]
  9. Choe H., Farzan M., Sun Y. 10 other authors 1996; The β -chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 85:1135–1148 [CrossRef]
    [Google Scholar]
  10. Cicala C., Arthos J., Ruiz M., Vaccarezza M., Rubbert A., Riva A., Wildt K., Cohen O., Fauci A. S. 1999; Induction of phosphorylation and intracellular association of CC chemokine receptor 5 and focal adhesion kinase in primary human CD4+ T cells by macrophage-tropic HIV envelope. J Immunol 163:420–426
    [Google Scholar]
  11. Cocchi F., DeVico A. L., Garzino-Demo A., Arya S. K., Gallo R. C., Lusso P. 1995; Identification of RANTES, MIP-1 α , and MIP-1 β as the major HIV-suppressive factors produced by CD8+ T cells. Science 270:1811–1815 [CrossRef]
    [Google Scholar]
  12. Cornelissen M., Mulder-Kampinga G., Veenstra J. 8 other authors 1995; Syncytium-inducing (SI) phenotype suppression at seroconversion after intramuscular inoculation of a non-syncytium-inducing/SI phenotypically mixed human immunodeficiency virus population. J Virol 69:1810–1818
    [Google Scholar]
  13. Distler O., McQueen P. W., Tsang M. L., Evans L. A., Hurren L., Byrne C., Penny R., Cooper D. A., Delaney S. F. 1995; Primary structure of the V3 region of gp120 from sequential human immunodeficiency virus type 1 isolates obtained from patients from the time of seroconversion. J Infect Dis 172:1384–1387 [CrossRef]
    [Google Scholar]
  14. Esser M. T., Bess J. W. Jr, Suryanarayana K., Chertova E., Marti D., Carrington M., Arthur L. O., Lifson J. D. 2001; Partial activation and induction of apoptosis in CD4+ and CD8+ T lymphocytes by conformationally authentic noninfectious human immunodeficiency virus type 1. J Virol 75:1152–1164 [CrossRef]
    [Google Scholar]
  15. Fenyö E. M., Morfeldt-Månson L., Chiodi F., Lind B., von Gegerfelt A., Albert J., Olausson E., Åsjö B. 1988; Distinct replicative and cytopathic characteristics of human immunodeficiency virus isolates. J Virol 62:4414–4419
    [Google Scholar]
  16. Gao W.-Y., Shirasaka T., Johns D. G., Broder S., Mitsuya H. 1993; Differential phosphorylation of azidothymidine, dideoxycytidine, and dideoxyinosine in resting and activated peripheral blood mononuclear cells. J Clin Invest 91:2326–2333 [CrossRef]
    [Google Scholar]
  17. Gao W.-Y., Agbaria R., Driscoll J. S., Mitsuya H. 1994; Divergent anti-human immunodeficiency virus activity and anabolic phosphorylation of 2′,3′-dideoxynucleoside analogs in resting and activated human cells. J Biol Chem 269:12633–12638
    [Google Scholar]
  18. Gondois-Rey F., Grivel J.-C., Biancotto A., Pion M., Vigne R., Margolis L. B., Hirsch I. 2002; Segregation of R5 and X4 HIV-1 variants to memory T cell subsets differentially expressing CD62L in ex vivo infected human lymphoid tissue. AIDS 16:1245–1249 [CrossRef]
    [Google Scholar]
  19. Greco G., Fujimura S. H., Mourich D. V., Levy J. A. 1999; Differential effects of human immunodeficiency virus isolates on β -chemokine and gamma interferon production and on cell proliferation. J Virol 73:1528–1534
    [Google Scholar]
  20. Hladik F., Lentz G., Akridge R. E., Peterson G., Kelley H., McElroy A., McElrath M. J. 1999; Dendritic cell-T-cell interactions support coreceptor-independent human immunodeficiency virus type 1 transmission in the human genital tract. J Virol 73:5833–5842
    [Google Scholar]
  21. Hoffman A. D., Banapour B., Levy J. A. 1985; Characterization of the AIDS-associated retrovirus reverse transcriptase and optimal conditions for its detection in virions. Virology 147:326–335 [CrossRef]
    [Google Scholar]
  22. Koot M., Vos A. H. V., Keet R. P. M., de Goede R. E. Y., 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]
  23. Koot M., Schellenkens P. T., Mulder J. W., Lange J. M., Roos M. T., Coutinho R. A., Tersmette M., Miedema F. 1993; Viral phenotype and T cell reactivity in human immunodeficiency virus type 1-infected asymptomatic men treated with zidovudine. J Infect Dis 168:733–736 [CrossRef]
    [Google Scholar]
  24. Korber B. T. M., Kunstman K. J., Patterson B. K., Furtado M., McEvilly M. M., Levy R., Wolinsky S. M. 1994; Genetic differences between blood- and brain-derived viral sequences from human immunodeficiency virus type 1-infected patients: evidence of conserved elements in the V3 region of the envelope protein of brain-derived sequences. J Virol 68:7467–7481
    [Google Scholar]
  25. Kreisberg J. F., Kwa D., Schramm B., Trautner V., Connor R., Schuitemaker H., Mullins J. I., van't Wout A. B., Goldsmith M. A. 2001; Cytopathicity of human immunodeficiency virus type 1 primary isolates depends on coreceptor usage and not patient disease status. J Virol 75:8842–8847 [CrossRef]
    [Google Scholar]
  26. Lawson V. A., Silburn K. A., Gorry P. R., Paukovic G., Purcell D. F. J., Greenway A. L., McPhee D. A. 2004; Apoptosis induced in synychronized human immunodeficiency virus type 1-infected primary peripheral blood mononuclear cells is detected after the peak of CD4+ T-lymphocyte loss and is dependent on the tropism of the gp120 envelope glycoprotein. Virology 327:70–82 [CrossRef]
    [Google Scholar]
  27. Liu Z.-Q., Wood C., Levy J. A., Cheng-Mayer C. 1990; The viral envelope gene is involved in macrophage tropism of a human immunodeficiency virus type 1 strain isolated from brain tissue. J Virol 64:6148–6153
    [Google Scholar]
  28. Mackewicz C. E., Ortega H. W., Levy J. A. 1991; CD8+ cell anti-HIV activity correlates with the clinical state of the infected individual. J Clin Invest 87:1462–1466 [CrossRef]
    [Google Scholar]
  29. Mackewicz C. E., Blackbourn D. J., Levy J. A. 1995; CD8+ cells suppress human immunodeficiency virus replication by inhibiting viral transcription. Proc Natl Acad Sci U S A 92:2308–2312 [CrossRef]
    [Google Scholar]
  30. Mackewicz C. E., Barker E., Greco G., Reyes-Teran G., Levy J. A. 1997; Do β -chemokines have clinical relevance in HIV infection?. J Clin Invest 100:921–930 [CrossRef]
    [Google Scholar]
  31. McDougal J. S., Cort S. P., Kennedy M. S., Cabridilla C. D., Feorino P. M., Francis D. P., Hicks D., Kalyanaraman V. S., Martin L. S. 1985; Immunoassay for the detection and quantitation of infectious human retrovirus, lymphadenopathy-associated virus (LAV). J Immunol Methods 76:171–183 [CrossRef]
    [Google Scholar]
  32. Meng G., Wei X., Wu X. 9 other authors 2002; Primary intestinal epithelial cells selectively transfer R5 HIV-1 to CCR5+ cells. Nat Med 8:150–156 [CrossRef]
    [Google Scholar]
  33. Nowak M. A. 1995; AIDS pathogenesis: from models to viral dynamics in patients. J Acquir Immune Defic Syndr Hum Retrovirol 10 (Suppl. 1):S1–S5 [CrossRef]
    [Google Scholar]
  34. Poli G., Fauci A. S. 1993; Cytokine modulation of HIV expression. Semin Immunol 5:165–173 [CrossRef]
    [Google Scholar]
  35. Popik W., Pitha P. M. 2000a; Exploitation of cellular signaling by HIV-1: unwelcome guests with master keys that signal their entry. Virology 276:1–6 [CrossRef]
    [Google Scholar]
  36. Popik W., Pitha P. M. 2000b; Inhibition of CD3/CD28-mediated activation of the MEK/ERK signaling pathway represses replication of X4 but not R5 human immunodeficiency virus type 1 in peripheral blood CD4+ T lymphocytes. J Virol 74:2558–2566 [CrossRef]
    [Google Scholar]
  37. Saag M. S., Hammer S. M., Lange J. M. A. 1994; Pathogenicity and diversity of HIV and implications for clinical management: a review. J Acquir Immune Defic Syndr 7 (Suppl. 2):S2–S10
    [Google Scholar]
  38. Schuitemaker H., Kootstra N. A., De Goede R. E. Y., De Wolf F., Miedema F., Tersmette M. 1991; Monocytotropic human immunodeficiency virus type 1 (HIV-1) variants detectable in all stages of HIV-1 infection lack T-cell line tropism and syncytium-inducing ability in primary T-cell culture. J Virol 65:356–363
    [Google Scholar]
  39. Shioda T., Levy J. A., Cheng-Mayer C. 1991; Macrophage and T cell-line tropisms of HIV-1 are determined by specific regions of the envelope gp120 gene. Nature 349:167–169 [CrossRef]
    [Google Scholar]
  40. Shioda T., Levy J. A., Cheng-Mayer C. 1992; Small amino acid changes in the V3 hypervariable region of gp120 can affect the T-cell-line and macrophage tropism of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A 89:9434–9438 [CrossRef]
    [Google Scholar]
  41. Shirasaka T., Chokekijchai S., Yamada A., Gosselin G., Imback J. L., Mitsuya H. 1995; Comparative analysis of anti-human immunodeficiency virus type 1 activities of dideoxynucleoside analogs in resting and activated peripheral blood mononuclear cells. Antimicrob Agents Chemother 39:2555–2559 [CrossRef]
    [Google Scholar]
  42. Tersmette M., de Goede R. E. Y., Al B. J. M., Winkel I. N., Gruters R. A., Cuypers H. T., Huisman H. G., Miedema F. 1988; Differential syncytium-inducing capacity of human immunodeficiency virus isolates: frequent detection of syncytium-inducing isolates in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. J Virol 62:2026–2032
    [Google Scholar]
  43. Tersmette M., Gruters R. A., de Wolf F., de Goede R. E. Y., Lange J. M. A., Schellekens P. T. A., Goudsmit J., Huisman H. G., Miedema F. 1989; Evidence for a role of virulent human immunodeficiency virus (HIV) variants in the pathogenesis of acquired immunodeficiency syndrome: studies on sequential HIV isolates. J Virol 63:2118–2125
    [Google Scholar]
  44. 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]
  45. van't Wout A. B., de Jong M. D., Kootstra N. A., Veenstra J., Lange J. M. A., Boucher C. A. B., Schuitemaker H. 1996; Changes in cellular virus load and zidovudine resistance of syncytium-inducing and non-syncytium-inducing human immunodeficiency virus populations under zidovudine pressure: a clonal analysis. J Infect Dis 174:845–849 [CrossRef]
    [Google Scholar]
  46. van't Wout A. B., Ran L. J., de Jong M. D. 10 other authors 1997; Selective inhibition of syncytium-inducing and nonsyncytium-inducing HIV-1 variants in individuals receiving didanosine or zidovudine, respectively. J Clin Invest 100:2325–2332 [CrossRef]
    [Google Scholar]
  47. Vanham G., Davis D., Willems B., Penne L., Kestens L., Janssens W., van der Groen G. 2000a; Dendritic cells, exposed to primary, mixed phenotype HIV-1 isolates preferentially, but not exclusively, replicate CCR5-using clones. AIDS 14:1874–1876 [CrossRef]
    [Google Scholar]
  48. Vanham G., Penne L., Allemeersch H., Kestens L., Willems B., van der Groen G., Jeang K.-T., Toossi Z., Rich E. 2000b; Modeling HIV transfer between dendritic cells and T cells: importance of HIV phenotype, dendritic cell-T cell contact and T-cell activation. AIDS 14:2299–2311 [CrossRef]
    [Google Scholar]
  49. Vicenzi E., Bordignon P. P., Biswas P., Brambilla A., Bovolenta C., Cota M., Sinigaglia F., Poli G. 1999; Envelope-dependent restriction of human immunodeficiency virus type 1 spreading in CD4+ T lymphocytes: R5 but not X4 viruses replicate in the absence of T-cell receptor restimulation. J Virol 73:7515–7523
    [Google Scholar]
  50. Wade C. M., Lobidel D., Leigh Brown A. J. 1998; Analysis of human immunodeficiency virus type 1 env and gag sequence variants derived from a mother and two vertically infected children provides evidence for the transmission of multiple sequence variants. J Gen Virol 79:1055–1068
    [Google Scholar]
  51. Zhu T., Mo H., Wang N., Nam D. S., Cao Y., Koup R. A., Ho D. D. 1993; Genotypic and phenotypic characterization of HIV-1 patients with primary infection. Science 261:1179–1181 [CrossRef]
    [Google Scholar]
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