Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1994 Oct;68(10):6634–6643. doi: 10.1128/jvi.68.10.6634-6643.1994

Variable course of primary simian immunodeficiency virus infection in lymph nodes: relation to disease progression.

L Chakrabarti 1, M C Cumont 1, L Montagnier 1, B Hurtrel 1
PMCID: PMC237084  PMID: 7916061

Abstract

To investigate the dynamics of spread of simian immunodeficiency virus (SIV) in the lymphoid organs, we sequentially analyzed the viral burden in lymph nodes (LN) of eight rhesus macaques inoculated intravenously with a high or low dose of the pathogenic SIVmac 251 isolate. For each animal, four axillary or inguinal LN were collected during the first weeks of infection and a fifth LN was taken 6 or 8 months later to estimate disease progression. Measurement of SIV RNA by in situ hybridization showed that all of the macaques studied had a phase of acute viral replication in LN between 7 and 14 days postinoculation which paralleled that observed in the blood. In a second phase, productive infection was controlled and viral particles were trapped in the germinal centers that developed in LN. While the peaks of productive infection were similar for the eight animals, marked differences in the numbers of productively infected cells that persisted in LN after primary infection were seen. Differences were less pronounced in the blood, where productive infection was efficiently controlled in all cases. The persistence of productively infected cells in LN after primary infection was found to be associated with more rapid disease progression, as measured by the decrease of the T4/T8 ratio and the occurrence of clinical signs. However, the persistence of a significant level of viral particles in germinal centers was observed even in animals that remained healthy over a 1- to 2-year observation period. This study indicates that the course of primary SIV infection in LN is variable, and it suggests that the initial capacity of the host to control productive infection in LN may determine the rate of disease progression.

Full text

PDF
6634

Images in this article

6636Image
on p.6636

Selected References

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

  1. Armstrong J. A., Horne R. Follicular dendritic cells and virus-like particles in AIDS-related lymphadenopathy. Lancet. 1984 Aug 18;2(8399):370–372. doi: 10.1016/s0140-6736(84)90540-3. [DOI] [PubMed] [Google Scholar]
  2. Biberfeld P., Chayt K. J., Marselle L. M., Biberfeld G., Gallo R. C., Harper M. E. HTLV-III expression in infected lymph nodes and relevance to pathogenesis of lymphadenopathy. Am J Pathol. 1986 Dec;125(3):436–442. [PMC free article] [PubMed] [Google Scholar]
  3. Brahic M., Haase A. T., Cash E. Simultaneous in situ detection of viral RNA and antigens. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5445–5448. doi: 10.1073/pnas.81.17.5445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burke A. P., Benson W., Ribas J. L., Anderson D., Chu W. S., Smialek J., Virmani R. Postmortem localization of HIV-1 RNA by in situ hybridization in lymphoid tissues of intravenous drug addicts who died unexpectedly. Am J Pathol. 1993 Jun;142(6):1701–1713. [PMC free article] [PubMed] [Google Scholar]
  5. Chakrabarti L., Guyader M., Alizon M., Daniel M. D., Desrosiers R. C., Tiollais P., Sonigo P. Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses. Nature. 1987 Aug 6;328(6130):543–547. doi: 10.1038/328543a0. [DOI] [PubMed] [Google Scholar]
  6. Chakrabarti L., Isola P., Cumont M. C., Claessens-Maire M. A., Hurtrel M., Montagnier L., Hurtrel B. Early stages of simian immunodeficiency virus infection in lymph nodes. Evidence for high viral load and successive populations of target cells. Am J Pathol. 1994 Jun;144(6):1226–1237. [PMC free article] [PubMed] [Google Scholar]
  7. Chalifoux L. V., Ringler D. J., King N. W., Sehgal P. K., Desrosiers R. C., Daniel M. D., Letvin N. L. Lymphadenopathy in macaques experimentally infected with the simian immunodeficiency virus (SIV). Am J Pathol. 1987 Jul;128(1):104–110. [PMC free article] [PubMed] [Google Scholar]
  8. Connor R. I., Mohri H., Cao Y., Ho D. D. Increased viral burden and cytopathicity correlate temporally with CD4+ T-lymphocyte decline and clinical progression in human immunodeficiency virus type 1-infected individuals. J Virol. 1993 Apr;67(4):1772–1777. doi: 10.1128/jvi.67.4.1772-1777.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Daniel M. D., Letvin N. L., King N. W., Kannagi M., Sehgal P. K., Hunt R. D., Kanki P. J., Essex M., Desrosiers R. C. Isolation of T-cell tropic HTLV-III-like retrovirus from macaques. Science. 1985 Jun 7;228(4704):1201–1204. doi: 10.1126/science.3159089. [DOI] [PubMed] [Google Scholar]
  10. Dierich M. P., Ebenbichler C. F., Marschang P., Füst G., Thielens N. M., Arlaud G. J. HIV and human complement: mechanisms of interaction and biological implication. Immunol Today. 1993 Sep;14(9):435–440. doi: 10.1016/0167-5699(93)90246-H. [DOI] [PubMed] [Google Scholar]
  11. Embretson J., Zupancic M., Ribas J. L., Burke A., Racz P., Tenner-Racz K., Haase A. T. Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature. 1993 Mar 25;362(6418):359–362. doi: 10.1038/362359a0. [DOI] [PubMed] [Google Scholar]
  12. Fauci A. S. Multifactorial nature of human immunodeficiency virus disease: implications for therapy. Science. 1993 Nov 12;262(5136):1011–1018. doi: 10.1126/science.8235617. [DOI] [PubMed] [Google Scholar]
  13. Fox C. H., Cottler-Fox M. The pathobiology of HIV infection. Immunol Today. 1992 Sep;13(9):353–356. doi: 10.1016/0167-5699(92)90171-3. [DOI] [PubMed] [Google Scholar]
  14. Fox C. H., Tenner-Rácz K., Rácz P., Firpo A., Pizzo P. A., Fauci A. S. Lymphoid germinal centers are reservoirs of human immunodeficiency virus type 1 RNA. J Infect Dis. 1991 Dec;164(6):1051–1057. doi: 10.1093/infdis/164.6.1051. [DOI] [PubMed] [Google Scholar]
  15. Gerdes J., Flad H. D. Follicular dendritic cells and their role in HIV infection. Immunol Today. 1992 Mar;13(3):81–83. doi: 10.1016/0167-5699(92)90145-W. [DOI] [PubMed] [Google Scholar]
  16. Joling P., van Wichen D. F., Parmentier H. K., Biberfeld P., Böttiger D., Tschopp J., Rademakers L. H., Schuurman H. J. Simian immunodeficiency virus (SIVsm) infection of cynomolgus monkeys: effects on follicular dendritic cells in lymphoid tissue. AIDS Res Hum Retroviruses. 1992 Dec;8(12):2021–2030. doi: 10.1089/aid.1992.8.2021. [DOI] [PubMed] [Google Scholar]
  17. Kannagi M., Kiyotaki M., Desrosiers R. C., Reimann K. A., King N. W., Waldron L. M., Letvin N. L. Humoral immune responses to T cell tropic retrovirus simian T lymphotropic virus type III in monkeys with experimentally induced acquired immune deficiency-like syndrome. J Clin Invest. 1986 Nov;78(5):1229–1236. doi: 10.1172/JCI112706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Lafeuillade A., Tamalet C., Pellegrino P., Tourres C., Yahi N., Vignoli C., Quilichini R., de Micco P. High viral burden in lymph nodes during early stages of HIV-1 infection. AIDS. 1993 Nov;7(11):1527–1528. doi: 10.1097/00002030-199311000-00019. [DOI] [PubMed] [Google Scholar]
  20. Letvin N. L., King N. W. Immunologic and pathologic manifestations of the infection of rhesus monkeys with simian immunodeficiency virus of macaques. J Acquir Immune Defic Syndr. 1990;3(11):1023–1040. [PubMed] [Google Scholar]
  21. Pantaleo G., Graziosi C., Demarest J. F., Butini L., Montroni M., Fox C. H., Orenstein J. M., Kotler D. P., Fauci A. S. HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature. 1993 Mar 25;362(6418):355–358. doi: 10.1038/362355a0. [DOI] [PubMed] [Google Scholar]
  22. Parmentier H. K., van Wichen D., Sie-Go D. M., Goudsmit J., Borleffs J. C., Schuurman H. J. HIV-1 infection and virus production in follicular dendritic cells in lymph nodes. A case report, with analysis of isolated follicular dendritic cells. Am J Pathol. 1990 Aug;137(2):247–251. [PMC free article] [PubMed] [Google Scholar]
  23. Popov J., McGraw T., Hofmann B., Vowels B., Shum A., Nishanian P., Fahey J. L. Acute lymphoid changes and ongoing immune activation in SIV infection. J Acquir Immune Defic Syndr. 1992;5(4):391–399. [PubMed] [Google Scholar]
  24. Reimann K. A., Tenner-Racz K., Racz P., Montefiori D. C., Yasutomi Y., Lin W., Ransil B. J., Letvin N. L. Immunopathogenic events in acute infection of rhesus monkeys with simian immunodeficiency virus of macaques. J Virol. 1994 Apr;68(4):2362–2370. doi: 10.1128/jvi.68.4.2362-2370.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ringler D. J., Wyand M. S., Walsh D. G., MacKey J. J., Chalifoux L. V., Popovic M., Minassian A. A., Sehgal P. K., Daniel M. D., Desrosiers R. C. Cellular localization of simian immunodeficiency virus in lymphoid tissues. I. Immunohistochemistry and electron microscopy. Am J Pathol. 1989 Feb;134(2):373–383. [PMC free article] [PubMed] [Google Scholar]
  26. Rosenberg Y. J., Shafferman A., White B. D., Papermaster S. F., Leon E., Eddy G. A., Benveniste R., Burke D. S., Lewis M. G. Variation in the CD4+ and CD8+ populations in lymph nodes does not reflect that in the blood during SIVMNE/E11S infection of macaques. J Med Primatol. 1992 Feb-May;21(2-3):131–137. [PubMed] [Google Scholar]
  27. Saksela K., Muchmore E., Girard M., Fultz P., Baltimore D. High viral load in lymph nodes and latent human immunodeficiency virus (HIV) in peripheral blood cells of HIV-1-infected chimpanzees. J Virol. 1993 Dec;67(12):7423–7427. doi: 10.1128/jvi.67.12.7423-7427.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Saksela K., Stevens C., Rubinstein P., Baltimore D. Human immunodeficiency virus type 1 mRNA expression in peripheral blood cells predicts disease progression independently of the numbers of CD4+ lymphocytes. Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1104–1108. doi: 10.1073/pnas.91.3.1104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schriever F., Nadler L. M. The central role of follicular dendritic cells in lymphoid tissues. Adv Immunol. 1992;51:243–284. doi: 10.1016/s0065-2776(08)60489-7. [DOI] [PubMed] [Google Scholar]
  30. Schuurman H. J., Krone W. J., Broekhuizen R., Goudsmit J. Expression of RNA and antigens of human immunodeficiency virus type-1 (HIV-1) in lymph nodes from HIV-1 infected individuals. Am J Pathol. 1988 Dec;133(3):516–524. [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Spiegel H., Herbst H., Niedobitek G., Foss H. D., Stein H. Follicular dendritic cells are a major reservoir for human immunodeficiency virus type 1 in lymphoid tissues facilitating infection of CD4+ T-helper cells. Am J Pathol. 1992 Jan;140(1):15–22. [PMC free article] [PubMed] [Google Scholar]
  33. Tenner-Racz K., Racz P., Bofill M., Schulz-Meyer A., Dietrich M., Kern P., Weber J., Pinching A. J., Veronese-Dimarzo F., Popovic M. HTLV-III/LAV viral antigens in lymph nodes of homosexual men with persistent generalized lymphadenopathy and AIDS. Am J Pathol. 1986 Apr;123(1):9–15. [PMC free article] [PubMed] [Google Scholar]
  34. Tindall B., Cooper D. A. Primary HIV infection: host responses and intervention strategies. AIDS. 1991 Jan;5(1):1–14. [PubMed] [Google Scholar]
  35. Venet A., Bourgault I., Aubertin A. M., Kiény M. P., Levy J. P. Cytotoxic T lymphocyte response against multiple simian immunodeficiency virusA (SIV) proteins in SIV-infected macaques. J Immunol. 1992 May 1;148(9):2899–2908. [PubMed] [Google Scholar]
  36. Wyand M. S., Ringler D. J., Naidu Y. M., Mattmuller M., Chalifoux L. V., Sehgal P. K., Daniel M. D., Desrosiers R. C., King N. W. Cellular localization of simian immunodeficiency virus in lymphoid tissues. II. In situ hybridization. Am J Pathol. 1989 Feb;134(2):385–393. [PMC free article] [PubMed] [Google Scholar]
  37. Zhang J. Y., Martin L. N., Watson E. A., Montelaro R. C., West M., Epstein L., Murphey-Corb M. Simian immunodeficiency virus/delta-induced immunodeficiency disease in rhesus monkeys: relation of antibody response and antigenemia. J Infect Dis. 1988 Dec;158(6):1277–1286. doi: 10.1093/infdis/158.6.1277. [DOI] [PubMed] [Google Scholar]

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

RESOURCES