1887

Abstract

A better understanding of virological events during the early phase of human immunodeficiency virus 1 (HIV-1) infection is important for development of effective antiviral vaccines. In this study, by using quantitative PCR and an infectious plaque assay, virus distribution and replication were examined in various internal organs of rhesus macaques for almost 1 month after intrarectal inoculation of a pathogenic simian immunodeficiency virus/HIV chimeric virus (SHIV-C2/1-KS661c). At 3 days post-inoculation (p.i.), proviral DNA was detected in the rectum, thymus and axillary lymph node. In lymphoid tissues, infectious virus was first detected at 6 days p.i. and a high level of proviral DNA and infectious virus were both detected at 13 days p.i. By 27 days p.i., levels of infectious virus decreased dramatically, although proviral DNA load remained unaltered. In the intestinal tract, levels of infectious virus detected were much lower than in lymphoid tissues, whereas proviral DNA was detected at the same level as in lymphoid tissues throughout the infection. In the thymus and jejunum, CD4CD8 double-positive T cells were depleted earlier than CD4 single-positive cells. These results show that the virus spread quickly to systemic tissues after mucosal transmission. Thereafter, infectious virus was actively produced in the lymphoid tissues, but levels decreased significantly after the peak of viraemia. In contrast, in the intestinal tract, infectious virus was produced at low levels from the beginning of infection. Moreover, virus pathogenesis differed in CD4 single-positive and CD4CD8 double-positive T cells.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81307-0
2006-05-01
2019-11-15
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/5/1311.html?itemId=/content/journal/jgv/10.1099/vir.0.81307-0&mimeType=html&fmt=ahah

References

  1. Baum, L. L., Cassutt, K. J., Knigge, K. & 7 other authors ( 1996; ). HIV-1 gp120-specific antibody-dependent cell-mediated cytotoxicity correlates with rate of disease progression. J Immunol 157, 2168–2173.
    [Google Scholar]
  2. Brenchley, J. M., Schacker, T. W., Ruff, L. E. & 8 other authors ( 2004; ). CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 200, 749–759.[CrossRef]
    [Google Scholar]
  3. Cantó-Nogués, C., Jones, S., Sangster, R. & 8 other authors ( 2001; ). In situ hybridization and immunolabelling study of the early replication of simian immunodeficiency virus (SIVmacJ5) in vivo. J Gen Virol 82, 2225–2234.
    [Google Scholar]
  4. Centlivre, M., Sommer, P., Michel, M. & 8 other authors ( 2005; ). HIV-1 clade promoters strongly influence spatial and temporal dynamics of viral replication in vivo. J Clin Invest 115, 348–358.[CrossRef]
    [Google Scholar]
  5. Chun, T.-W., Carruth, L., Finzi, D. & 12 other authors ( 1997; ). Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 387, 183–188.[CrossRef]
    [Google Scholar]
  6. Clapham, P. R., Weiss, R. A., Dalgleish, A. G., Exley, M., Whitby, D. & Hogg, N. ( 1987; ). Human immunodeficiency virus infection of monocytic and T-lymphocytic cells: receptor modulation and differentiation induced by phorbol ester. Virology 158, 44–51.[CrossRef]
    [Google Scholar]
  7. Couëdel-Courteille, A., Butor, C., Juillard, V., Guillet, J.-G. & Venet, A. ( 1999; ). Dissemination of SIV after rectal infection preferentially involves paracolic germinal centers. Virology 260, 277–294.[CrossRef]
    [Google Scholar]
  8. Couëdel-Courteille, A., Prétet, J.-L., Barget, N., Jacques, S., Petitprez, K., Tulliez, M., Guillet, J.-G., Venet, A. & Butor, C. ( 2003; ). Delayed viral replication and CD4+ T cell depletion in the rectosigmoid mucosa of macaques during primary rectal SIV infection. Virology 316, 290–301.[CrossRef]
    [Google Scholar]
  9. Dalgleish, A. G., Beverley, P. C., Clapham, P. R., Crawford, D. H., Greaves, M. F. & Weiss, R. A. ( 1984; ). The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312, 763–767.[CrossRef]
    [Google Scholar]
  10. Fauci, A. S. ( 1996; ). Host factors in the pathogenesis of HIV disease. Antibiot Chemother 48, 4–12.
    [Google Scholar]
  11. Fehniger, T. A., Herbein, G., Yu, H., Para, M. I., Bernstein, Z. P., O'Brien, W. A. & Caligiuri, M. A. ( 1998; ). Natural killer cells from HIV-1+ patients produce C-C chemokines and inhibit HIV-1 infection. J Immunol 161, 6433–6438.
    [Google Scholar]
  12. Harouse, J. M., Gettie, A., Tan, R. C. H., Blanchard, J. & Cheng-Mayer, C. ( 1999; ). Distinct pathogenic sequela in rhesus macaques infected with CCR5 or CXCR4 utilizing SHIVs. Science 284, 816–819.[CrossRef]
    [Google Scholar]
  13. Haynes, B. F., Denning, S. M., Le, P. T. & Singer, K. H. ( 1990; ). Human intrathymic T cell differentiation. Semin Immunol 2, 67–77.
    [Google Scholar]
  14. Hirsch, V. M., Sharkey, M. E., Brown, C. R. & 8 other authors ( 1998; ). Vpx is required for dissemination and pathogenesis of SIVSM PBj: evidence of macrophage-dependent viral amplification. Nat Med 4, 1401–1408.[CrossRef]
    [Google Scholar]
  15. Hori, T., Cupp, J., Wrighton, N., Lee, F. & Spits, H. ( 1991; ). Identification of a novel human thymocyte subset with a phenotype of CD3− CD4+ CD8 alpha+beta-1. Possible progeny of the CD3− CD4− CD8− subset. J Immunol 146, 4078–4084.
    [Google Scholar]
  16. Hu, J., Gardner, M. B. & Miller, C. J. ( 2000; ). Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells. J Virol 74, 6087–6095.[CrossRef]
    [Google Scholar]
  17. Joag, S. V., Adany, I., Li, Z., Foresman, L., Pinson, D. M., Wang, C., Stephens, E. B., Raghavan, R. & Narayan, O. ( 1997; ). Animal model of mucosally transmitted human immunodeficiency virus type 1 disease: intravaginal and oral deposition of simian/human immunodeficiency virus in macaques results in systemic infection, elimination of CD4+ T cells, and AIDS. J Virol 71, 4016–4023.
    [Google Scholar]
  18. Kato, S., Hiraishi, Y., Nishimura, N., Sugita, T., Tomihama, M. & Takano, T. ( 1998; ). A plaque hybridization assay for quantifying and cloning infectious human immunodeficiency virus type 1 virions. J Virol Methods 72, 1–7.[CrossRef]
    [Google Scholar]
  19. Klatzmann, D., Champagne, E., Chamaret, S., Gruest, J., Guetard, D., Hercend, T., Gluckman, J. C. & Montagnier, L. ( 1984; ). T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 312, 767–768.[CrossRef]
    [Google Scholar]
  20. Kottilil, S., Chun, T.-W., Moir, S., Liu, S., McLaughlin, M., Hallahan, C. W., Maldarelli, F., Corey, L. & Fauci, A. S. ( 2003; ). Innate immunity in human immunodeficiency virus infection: effect of viremia on natural killer cell function. J Infect Dis 187, 1038–1045.[CrossRef]
    [Google Scholar]
  21. Levy, J. A. ( 2001; ). The importance of the innate immune system in controlling HIV infection and disease. Trends Immunol 22, 312–316.[CrossRef]
    [Google Scholar]
  22. Li, Q., Duan, L., Estes, J. D. & 7 other authors ( 2005; ). Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature 434, 1148–1152.
    [Google Scholar]
  23. Lu, Y., Pauza, C. D., Lu, X., Montefiori, D. C. & Miller, C. J. ( 1998; ). Rhesus macaques that become systemically infected with pathogenic SHIV 89.6-PD after intravenous, rectal, or vaginal inoculation and fail to make an antiviral antibody response rapidly develop AIDS. J Acquir Immune Defic Syndr Hum Retrovirol 19, 6–18.[CrossRef]
    [Google Scholar]
  24. Lundqvist, C., Baranov, V., Hammarstrom, S., Athlin, L. & Hammarstrom, M. L. ( 1995; ). Intra-epithelial lymphocytes. Evidence for regional specialization and extrathymic T cell maturation in the human gut epithelium. Int Immunol 7, 1473–1487.[CrossRef]
    [Google Scholar]
  25. Mattapallil, J. J., Reay, E. & Dandekar, S. ( 2000; ). An early expansion of CD8αβ T cells, but depletion of resident CD8αα T cells, occurs in the intestinal epithelium during primary simian immunodeficiency virus infection. AIDS 14, 637–646.[CrossRef]
    [Google Scholar]
  26. Mattapallil, J. J., Douek, D. C., Hill, B., Nishimura, Y., Martin, M. & Roederer, M. ( 2005; ). Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 434, 1093–1097.[CrossRef]
    [Google Scholar]
  27. Mehandru, S., Poles, M. A., Tenner-Racz, K., Horowitz, A., Hurley, A., Hogan, C., Boden, D., Racz, P. & Markowitz, M. ( 2004; ). Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med 200, 761–770.[CrossRef]
    [Google Scholar]
  28. Mellors, J. W., Kingsley, L. A., Rinaldo, C. R., Jr, Todd, J. A., Hoo, B. S., Kokka, R. P. & Gupta, P. ( 1995; ). Quantitation of HIV-1 RNA in plasma predicts outcome after seroconversion. Ann Intern Med 122, 573–579.[CrossRef]
    [Google Scholar]
  29. Miller, C. J., Li, Q., Abel, K. & 12 other authors ( 2005; ). Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus. J Virol 79, 9217–9227.[CrossRef]
    [Google Scholar]
  30. Milush, J. M., Kosub, D., Marthas, M., Schmidt, K., Scott, F., Wozniakowski, A., Brown, C., Westmoreland, S. & Sodora, D. L. ( 2004; ). Rapid dissemination of SIV following oral inoculation. AIDS 18, 2371–2380.
    [Google Scholar]
  31. Miyake, A., Enose, Y., Ohkura, S., Suzuki, H., Kuwata, T., Shimada, T., Kato, S., Narayan, O. & Hayami, M. ( 2004; ). The quantity and diversity of infectious viruses in various tissues of SHIV-infected monkeys at the early and AIDS stages. Arch Virol 149, 943–955.[CrossRef]
    [Google Scholar]
  32. Oliva, A., Kinter, A. L., Vaccarezza, M. & 10 other authors ( 1998; ). Natural killer cells from human immunodeficiency virus (HIV)-infected individuals are an important source of CC-chemokines and suppress HIV-1 entry and replication in vitro. J Clin Invest 102, 223–231.[CrossRef]
    [Google Scholar]
  33. O'Neil, S. P., Mossman, S. P., Maul, D. H. & Hoover, E. A. ( 1999; ). In vivo cell and tissue tropism of SIVsmmPBj14-bcl.3. AIDS Res Hum Retroviruses 15, 203–215.[CrossRef]
    [Google Scholar]
  34. Reyes, R. A., Canfield, D. R., Esser, U., Adamson, L. A., Brown, C. R., Cheng-Mayer, C., Gardner, M. B., Harouse, J. M. & Luciw, P. A. ( 2004; ). Induction of simian AIDS in infant rhesus macaques infected with CCR5- or CXCR4-utilizing simian-human immunodeficiency viruses is associated with distinct lesions of the thymus. J Virol 78, 2121–2130.[CrossRef]
    [Google Scholar]
  35. Rosenzweig, M., Connole, M., Forand-Barabasz, A., Tremblay, M.-P., Johnson, R. P. & Lackner, A. A. ( 2000; ). Mechanisms associated with thymocyte apoptosis induced by simian immunodeficiency virus. J Immunol 165, 3461–3468.[CrossRef]
    [Google Scholar]
  36. Sattentau, Q. J., Clapham, P. R., Weiss, R. A., Beverley, P. C., Montagnier, L., Alhalabi, M. F., Gluckmann, J. C. & Klatzmann, D. ( 1988; ). The human and simian immunodeficiency viruses HIV-1, HIV-2 and SIV interact with similar epitopes on their cellular receptor, the CD4 molecule. AIDS 2, 101–105.[CrossRef]
    [Google Scholar]
  37. Schacker, T., Collier, A. C., Hughes, J., Shea, T. & Corey, L. ( 1996; ). Clinical and epidemiologic features of primary HIV infection. Ann Intern Med 125, 257–264.[CrossRef]
    [Google Scholar]
  38. Schnittman, S. M., Denning, S. M., Greenhouse, J. J., Justement, J. S., Baseler, M., Kurtzberg, J., Haynes, B. F. & Fauci, A. S. ( 1990; ). Evidence for susceptibility of intrathymic T-cell precursors and their progeny carrying T-cell antigen receptor phenotypes TCRαβ + and TCRγδ + to human immunodeficiency virus infection: a mechanism for CD4+ (T4) lymphocyte depletion. Proc Natl Acad Sci U S A 87, 7727–7731.[CrossRef]
    [Google Scholar]
  39. Sei, S., Kleiner, D. E., Kopp, J. B., Chandra, R., Klotman, P. E., Yarchoan, R., Pizzo, P. A. & Mitsuya, H. ( 1994; ). Quantitative analysis of viral burden in tissues from adults and children with symptomatic human immunodeficiency virus type 1 infection assessed by polymerase chain reaction. J Infect Dis 170, 325–333.[CrossRef]
    [Google Scholar]
  40. Shinohara, K., Sakai, K., Ando, S. & 10 other authors ( 1999; ). A highly pathogenic simian/human immunodeficiency virus with genetic changes in cynomolgus monkey. J Gen Virol 80, 1231–1240.
    [Google Scholar]
  41. Smit-McBride, Z., Mattapallil, J. J., McChesney, M., Ferrick, D. & Dandekar, S. ( 1998; ). Gastrointestinal T lymphocytes retain high potential for cytokine responses but have severe CD4+ T-cell depletion at all stages of simian immunodeficiency virus infection compared to peripheral lymphocytes. J Virol 72, 6646–6656.
    [Google Scholar]
  42. Spira, A. I., Marx, P. A., Patterson, B. K., Mahoney, J., Koup, R. A., Wolinsky, S. M. & Ho, D. D. ( 1996; ). Cellular targets of infection and route of viral dissemination after an intravaginal inoculation of simian immunodeficiency virus into rhesus macaques. J Exp Med 183, 215–225.[CrossRef]
    [Google Scholar]
  43. Stahl-Hennig, C., Steinman, R. M., Tenner-Racz, K. & 7 other authors ( 1999; ). Rapid infection of oral mucosal-associated lymphoid tissue with simian immunodeficiency virus. Science 285, 1261–1265.[CrossRef]
    [Google Scholar]
  44. Suryanarayana, K., Wiltrout, T. A., Vasquez, G. M., Hirsch, V. M. & Lifson, J. D. ( 1998; ). Plasma SIV RNA viral load determination by real-time quantification of product generation in reverse transcriptase-polymerase chain reaction. AIDS Res Hum Retroviruses 14, 183–189.[CrossRef]
    [Google Scholar]
  45. Veazey, R. S., Rosenzweig, M., Shvetz, D. E., Pauley, D. R., DeMaria, M., Chalifoux, L. V., Johnson, R. P. & Lackner, A. A. ( 1997; ). Characterization of gut-associated lymphoid tissue (GALT) of normal rhesus macaques. Clin Immunol Immunopathol 82, 230–242.[CrossRef]
    [Google Scholar]
  46. Veazey, R. S., DeMaria, M., Chalifoux, L. V. & 7 other authors ( 1998; ). Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 280, 427–431.[CrossRef]
    [Google Scholar]
  47. Veazey, R. S., Mansfield, K. G., Tham, I. C., Carville, A. C., Shvetz, D. E., Forand, A. E. & Lackner, A. A. ( 2000a; ). Dynamics of CCR5 expression by CD4+ T cells in lymphoid tissues during simian immunodeficiency virus infection. J Virol 74, 11001–11007.[CrossRef]
    [Google Scholar]
  48. Veazey, R. S., Tham, I. C., Mansfield, K. G., DeMaria, M., Forand, A. E., Shvetz, D. E., Chalifoux, L. V., Sehgal, P. K. & Lackner, A. A. (2000b; ). Identifying the target cell in primary simian immunodeficiency virus (SIV) infection: highly activated memory CD4+ T cells are rapidly eliminated in early SIV infection in vivo. J Virol 74, 57–64.[CrossRef]
    [Google Scholar]
  49. Zhang, Z.-Q., Schuler, T., Zupancic, M. & 21 other authors ( 1999; ). Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells. Science 286, 1353–1357.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81307-0
Loading
/content/journal/jgv/10.1099/vir.0.81307-0
Loading

Data & Media loading...

Most Cited This Month

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