hybridization and immunolabelling study of the early replication of simian immunodeficiency virus (SIVmacJ5) Free

Abstract

The distribution of virus-infected cells in cynomolgus macaques was determined at 4, 7, 14 and 28 days following intravenous challenge with 1000 TCID of the wild-type simian immunodeficiency virus SIVmacJ5 (stock J5C). At each time-point, pairs of macaques were killed humanely and the presence of SIV was determined and quantified in blood, spleen, peripheral and mesenteric lymph nodes, thymus, lung and ileum by virus co-cultivation with C8166 cells, by quantitative DNA PCR or by hybridization (ISH). At day 4 post-infection (p.i.), detection of the virus was sporadic. By day 7 p.i., however, significant SIV loads were detected in the blood and lymphoid tissues by DNA PCR and virus co-cultivation. Large numbers of cells expressing SIV RNA were detected in mesenteric lymph nodes by ISH and significantly fewer (<0·05) in the spleen. Significant numbers of ISH-positive cells were also observed in sections of ileum. By day 14 p.i., the distribution of SIV was more even in all lymphoid tissues analysed. By day 28, most of the tissues were negative by ISH, but all remained positive by virus isolation and DNA PCR. Immunolabelling of sections of mesenteric lymph node with monoclonal antibodies specific for SIV envelope and Nef largely confirmed the observations from ISH. These results indicate that, even following intravenous challenge, a major site of the initial replication of SIV is gut-associated lymphoid tissue. Vaccines that induce protection at this site may therefore be superior, even against parenteral challenge.

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2001-09-01
2024-03-28
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References

  1. Almond N. M., Heeney J. L. 1998; AIDS vaccine development in primate models. AIDS 12:S133–S140
    [Google Scholar]
  2. Almond N., Stott J. 1999; Live attenuated SIV – a model of a vaccine for AIDS. Immunology Letters 66:167–170
    [Google Scholar]
  3. Almond N., Kent K., Cranage M., Rud E., Clarke B., Stott E. J. 1995; Protection by attenuated simian immunodeficiency virus in macaques against challenge with virus-infected cells. Lancet 345:1342–1344
    [Google Scholar]
  4. An S. F., Franklin D., Fleming K. A. 1992; Generation of digoxigenin-labelled double-stranded and single-stranded probes using the polymerase chain reaction. Molecular and Cellular Probes 6:193–200
    [Google Scholar]
  5. Arnold C., Jenkins A., Almond N., Stott E. J., Kent K. A. 1999; Monoclonal antibodies recognize at least five epitopes on the SIV Nef protein and identify an in vitro-induced mutation. AIDS Research and Human Retroviruses 15:1087–1097
    [Google Scholar]
  6. Baskin G. B., Martin L. N., Murphey-Corb M., Hu F.-S., Kuebler D., Davison B. 1995; Distribution of SIV in lymph nodes of serially sacrificed rhesus monkeys. AIDS Research and Human Retroviruses 11:273–285
    [Google Scholar]
  7. Cao Y., Qin L., Zhang L., Safrit J., Ho D. D. 1995; Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. New England Journal of Medicine 332:201–208
    [Google Scholar]
  8. Chakrabarti L., Cumont M.-C., Montagnier L., Hurtrel B. 1994a; Variable course of primary simian immunodeficiency virus infection in lymph nodes: relation to disease progression. Journal of Virology 68:6634–6643
    [Google Scholar]
  9. Chakrabarti L., Isola P., Cumont M.-C., Claessens-Maire M.-A., Hurtrel M., Montagnier L., Hurtrel B. 1994b; Early stages of simian immunodeficiency virus infection in lymph nodes. Evidence for high viral load and successive populations of target cells. American Journal of Pathology 144:1226–1237
    [Google Scholar]
  10. Cranage M. P., Whatmore A. M., Sharpe S. A., Cook N., Polyanskaya N., Leech S., Smith J. D., Rud E. W., Dennis M. J., Hall G. A. 1997; Macaques infected with live attenuated SIVmac are protected against superinfection via the rectal mucosa. Virology 229:143–154
    [Google Scholar]
  11. Kent K. A., Gritz L., Stallard G., Cranage M. P., Collignon C., Thiriart C., Corcoran T., Silvera P., Stott E. J. 1991; Production and characterisation of monoclonal antibodies to simian immunodeficiency virus envelope glycoproteins. AIDS 5:829–836
    [Google Scholar]
  12. Kent K. A., Kitchin P., Mills K. H., Page M., Taffs F., Corcoran T., Silvera P., Flanagan B., Powell C., Rose J., Ling C., Aubertin A.-M., Stott E. J. 1994; Passive immunization of cynomolgus macaques with immune sera or a pool of neutralizing monoclonal antibodies failed to protect against challenge with SIVmac251. AIDS Research and Human Retroviruses 10:189–194
    [Google Scholar]
  13. Lehner T., Wang Y.-F., Cranage M., Bergmeier L. A., Mitchell E., Tao L., Hall G., Dennis M., Cook N., Brookes R., Klavinskis L., Jones I., Doyle C., Ward R. 1996; Protective mucosal immunity elicited by targeted iliac lymph node immunization with a subunit SIV envelope and core vaccine in macaques. Nature Medicine 2:767–775
    [Google Scholar]
  14. Mellors J. W., Rinaldo C. R. Jr, Gupta P., White R. M., Todd J. A., Kingsley L. A. 1996; Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science 272:1167–1170
    [Google Scholar]
  15. Reimann K. A., Tenner-Racz K., Racz P., Montefiori D. C., Yasutomi Y., Lin W., Ransil B. J., Letvin N. L. 1994; Immunopathogenic events in acute infection of rhesus monkeys with simian immunodeficiency virus of macaques. Journal of Virology 68:2362–2370
    [Google Scholar]
  16. Reinhart T. A., Rogan M. J., Huddleston D., Rausch D. M., Eiden L. E., Haase A. T. 1997; Simian immunodeficiency virus burden in tissues and cellular compartments during clinical latency and AIDS. Journal of Infectious Diseases 176:1198–1208
    [Google Scholar]
  17. Rose J., Silvera P., Flanagan B., Kitchin P., Almond N. 1995; The development of PCR based assays for the detection and differentiation of simian immunodeficiency virus in vivo. Journal of Virological Methods 51:229–239
    [Google Scholar]
  18. Rud E. W., Cranage M., Yon J., Quirk J., Ogilvie L., Cook N., Webster S., Dennis M., Clarke B. E. 1994; Molecular and biological characterization of simian immunodeficiency virus macaque strain 32H proviral clones containing nef size variants. Journal of General Virology 75:529–543
    [Google Scholar]
  19. Schacker T., Little S., Connick E., Gebhard-Mitchell K., Zhang Z.-Q., Krieger J., Pryor J., Havlir D., Wong J. K., Richman D., Corey L., Haase A. T. 2000; Rapid accumulation of human immunodeficiency virus (HIV) in lymphatic tissue reservoirs during acute and early HIV infection: implications for timing of antiretroviral therapy. Journal of Infectious Diseases 181:354–357
    [Google Scholar]
  20. Simmonds P., Zhang L. Q., McOmish F., Balfe P., Ludlam C. A., Leigh-Brown A. J. 1991; 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. Journal of Virology 65:6266–6276
    [Google Scholar]
  21. Slade A., Jones S., Jenkins A., Bootman J., Heath A., Kitchin P., Almond N. 1995; Similar patterns of simian immunodeficiency virus env sequences are found in the blood and lymphoid tissues of chronically infected macaques. AIDS Research and Human Retroviruses 11:1509–1511
    [Google Scholar]
  22. 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. Journal of Virology 72:6646–6656
    [Google Scholar]
  23. Stahl-Hennig C., Steinman R. M., Tenner-Racz K., Pope M., Stolte N., Matz-Rensing K., Grobschupff G., Raschdorff B., Hunsmann G., Racz P. 1999; Rapid infection of oral mucosal-associated lymphoid tissue with simian immunodeficiency virus. Science 285:1261–1265
    [Google Scholar]
  24. Stott J., Almond N. 1995; Assessing animal models of AIDS. Nature Medicine 1:295–297
    [Google Scholar]
  25. Veazey R. S., DeMaria M., Chalifoux L. V., Shvetz D. E., Pauley D. R., Knight H. L., Rosenzweig M., Johnson R. P., Desrosiers R. C., Lackner A. A. 1998; Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 280:427–431
    [Google Scholar]
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