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A new approach to investigating the relationship between productive infection and cytopathicity in vivo

Nature Medicine volume 3, pages 218–221 (1997)Cite this article

Abstract

We describe a novel experimental approach to analyzing virus-host relationships and potential mechanisms of cytopathicity in vivo in simian immunodeficiency virus (SIV) infections. Progressive destruction of lymphoid tissue in the course of infection by SIV or human immunodeficiency virus (HIV) accompanies the loss of CD4+ T lymphocytes and sets the stage for AIDS1,2. Because one of the important early events in this pathological process is lysis of follicular dendritic cells3 (FDCs), we investigated the controversial role of productive SIV infection in the destruction of FDCs. To differentiate productive infections from the known association of virus with FDCs as immune complexes trapped on cell surfaces4–6, we used detection of spliced viral mRNAs in cells as evidence of productive infection. We found that spliced and unspliced viral RNAs could be detected by in situ hybridization (ISH) with specific antisense oligonucleotide probes in lymphocytes and macrophages with sensitivities of fewer than ten copies of spliced viral RNA per cell. We detected only unspliced RNA in germinal centers where FDCs reside. Thus, no productive infection of these cells can be detected in vivo by this assay, and their destruction likely occurs by indirect mechanisms that have yet to be determined.

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References

  1. Schuurman, H.-J. et al. Lymphocyte status of lymph node and blood in acquired immunodeficiency syndrome (AIDS) and AIDS-related complex disease. J. Pathol. 147, 269–280 (1985).

    Article  CAS  PubMed  Google Scholar 

  2. Diebold, J. et al. Lymph node modification in patients with the acquired immunodeficiency syndrome (AIDS) or with AIDS related complex (ARC). Pathol. Res. Pract. 180, 590–611 (1985).

    Article  CAS  PubMed  Google Scholar 

  3. Klaus, G.G.B., Humphrey, J.H., Kunkl, A. & Dongworth, D.W. The follicular dendritic Cell: Its role in antigen presentation in the generation of immunological memory. Immunol. Rev. 53, 3–18 (1980).

    Article  CAS  PubMed  Google Scholar 

  4. Mandel, T.E., Phipps, R.P., Abbot, A. & Tew, J.G. The follicular dendritic Cell: Long term antigen retention during immunity. Immunol. Rev. 53, 29–59 (1980).

    Article  CAS  PubMed  Google Scholar 

  5. Fox, C.H. et al. Lymphoid germinal centers are reservoirs of human immunodeficiency virus type 1 RNA. J. Infect. Dis. 164, 1051–1057 (1991).

    Article  CAS  PubMed  Google Scholar 

  6. Embretson, J.E. et al. Massive covert infection of helper T lymphocytes and macro-=phages by HIV during the incubation period of AIDS. Nature 362, 359–362 (1993).

    Article  CAS  PubMed  Google Scholar 

  7. Chakrabarti, L., Cumont, M.-C., Montagnier, L. & Hurtrel, B. Variable course of primary simian immunodeficiency virus infection in lymph nodes: Relation to disease progression. J. Virol. 68, 6634–6642 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Spiegel, H., Herbst, H., Niedobitek, G., F, 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. 140, 15–22 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Armstrong, J.A. & Home, R. Follicular dendritic Cells and virus-like particles in AIDS-related lymphadenopathy. Lancet 2, 370–372 (1984).

    Article  CAS  PubMed  Google Scholar 

  10. Cameron, P.U., Dawkins, R.L., Armstrong, J.A. & Bonifacio, E. Western blot profiles, lymph node ultrastructure and viral expression in HIV-infected patients: A correlative study. Clin. Exp. Immunol. 68, 465–478 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Sprenger, R. et al. Follicular dendritic Cells productively infected with immunodeficiency viruses transmit infection to T Cells. Med. Microbiol. Immunol. 184, 129–134 (1995).

    Article  CAS  PubMed  Google Scholar 

  12. Stahmer, I. et al. SIV infection of monkey spleen Cells including follicular dendritic Cells in different stages of disease. J. Acquir. Immun. Defic. Syndr. Hum. Retroviruses 11, 1–9 (1996).

    Article  CAS  Google Scholar 

  13. Parmentier, H.K. et al. HIV-1 infection and virus production in follicular dendritic Cells in lymph nodes. Am. J. Pathol. 137, 247–251 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Stahmer, I. et al. Isolation of normal human follicular dendritic Cells and CD4-independent in vitro infection by human immunodeficiency virus (HIV-1). Eur. J. Immunol 21, 1873–1878 (1991).

    Article  CAS  PubMed  Google Scholar 

  15. Schmitz, J. et al. Follicular dendritic Cells retain HIV-1 particles on their plasma membrane, but are not productively infected in asymptomatic patients with follicular hyperplasia. J. Immunol. 153, 1352–1359 (1994).

    CAS  PubMed  Google Scholar 

  16. Tenner-Racz, K., von Stemm, A.M.R., Gühlk, B., Schmitz, J. & Racz, P. Are follicular dendritic Cells, macrophages and interdigitating Cells of the lymphoid tissue productively infected by HIV?. Res. Virol. 145, 177–182 (1994).

    Article  CAS  PubMed  Google Scholar 

  17. Tsunoda, R., Hashimoto, K., Baba, M., Shigeta, S. & Sugai, N. Follicular dendritic Cells in vitro are not susceptible to infection by HIV-1. AIDS 10, 595–602 (1996).

    Article  CAS  PubMed  Google Scholar 

  18. Murphey-Corb, M. et al. Isolation of a HTLV-III-related retrovirus from macaques with simian AIDS and its possible origin in asymptomatic mangabeys. Nature 321, 435–437 (1986).

    Article  CAS  PubMed  Google Scholar 

  19. Murray, E., Rausch, D., Lendvay, J., Sharer, L. & Eiden, L. Cognitive and motor impairments associated with SIV infection in rhesus monkeys. Science 255, 1246–1249 (1992).

    Article  CAS  PubMed  Google Scholar 

  20. Rausch, D.M. et al. Cytopathologic and neurochemical correlates of progression to motor/cognitive impairment in SIV-infected rhesus monkeys. J. Neuropathol. Exp. Neural. 53, 165–175 (1994).

    Article  CAS  Google Scholar 

  21. Viglianti, G.A., Sharma, P.L., & Mullins, J.I. Simian immunodeficiency virus displays complex patterns of RNA splicing. J. Virol. 64, 4207–4216 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Haase, A.T. et al. Quantitative image analysis of HIV-1 infection in lymphoid tissue. Science 274, 985–989 (1996).

    Article  CAS  PubMed  Google Scholar 

  23. Heath, S.L., Tew, J.G., Tew, J.G., Szakal, A.K. & Burton, G.F. Follicular dendritic Cells and human immunodeficiency virus infectivity. Nature 377, 740–744 (1995).

    Article  CAS  PubMed  Google Scholar 

  24. Peng, H.-R. et al. Single Cell transcript analysis of human immunodeficiency virus gene expression in the transition from latent to productive infection. Virology 206, 16–27 (1995).

    Article  CAS  PubMed  Google Scholar 

  25. Reinhart, T.A., Rogan, M.J. & Haase, A.T. RNA splice site utilization by simian immunodeficiency viruses derived from sooty mangabey monkeys. Virology 224, 338–344 (1996).

    Article  CAS  PubMed  Google Scholar 

  26. Hirsch, V.M., Olmsted, R.A., Murphey-Corb, M., Purcell, R.H. & Johnson, P.R. An African primate lentivirus (SIVsm) closely related to HIV-2. Nature 339, 389 (1989).

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology, University of Minnesota Medical School, Box 196, 420 Delaware Street SE, Minneapolis, Minnesota, 55455, USA

    Todd A. Reinhart, Michael J. Rogan & Ashley T. Haase

  2. Department of Microbiology, Boston University School of Medicine, 80 South Concord Street, Boston, Massachusetts, 02118, USA

    Gregory A. Viglianti

  3. Laboratory of Cell Biology, National Institute of Mental Health, Building 36, Room 3A17, Bethesda, Maryland, 02815, USA

    Dianne M. Rausch & Lee E. Elden

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  1. Todd A. Reinhart
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  4. Dianne M. Rausch
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  6. Ashley T. Haase
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Reinhart, T., Rogan, M., Viglianti, G. et al. A new approach to investigating the relationship between productive infection and cytopathicity in vivo. Nat Med 3, 218–221 (1997). https://doi.org/10.1038/nm0297-218

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