1887

Abstract

CD8 T cells from human immunodeficiency virus (HIV)-infected individuals can suppress HIV replication in CD4 cells by a noncytotoxic mechanism that inhibits the expression of viral RNA. The present study examined whether other step(s) in the virus replicative cycle could be affected by the CD8 cells. Culturing HIV-infected CD4 T cells with antiviral CD8 T cells did not significantly reduce the amounts of (i) early HIV DNA reverse transcripts (detected by LTR-U3/R), (ii) total nuclear HIV DNA, or (iii) integrated proviral DNA. However, exposure to the CD8 T cells did cause a reduction in the amount of multiply spliced and full-length mRNA expressed by the infected CD4 T cells, confirming previous observations. The levels of glyceraldehyde-3-phosphate dehydrogenase and interleukin-2 receptor-α mRNA were not affected. The results support the conclusion that the noncytotoxic anti-HIV response of CD8 T cells, demonstrable , does not affect any of the virus replication steps leading to the integration of proviral HIV, but specifically interrupts the expression of viral RNA.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-81-5-1261
2000-05-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/81/5/0811261a.html?itemId=/content/journal/jgv/10.1099/0022-1317-81-5-1261&mimeType=html&fmt=ahah

References

  1. Barker, E., Bossart, K. N., Locher, C. P., Patterson, B. K. & Levy, J. A. (1996). CD8+ cells from asymptomatic human immunodeficiency virus-infected individuals suppress superinfection of their peripheral blood mononuclear cells.Journal of General Virology 77, 2953-2962.[CrossRef] [Google Scholar]
  2. Chen, C. H., Weinhold, K. J., Bartlett, J. A., Bolognesi, D. P. & Greenberg, M. L. (1993). CD8+ T lymphocyte-mediated inhibition of HIV-1 long terminal repeat transcription: a novel antiviral mechanism.AIDS Research and Human Retroviruses 9, 1079-1086.[CrossRef] [Google Scholar]
  3. Chun, T.-W., Carruth, L., Finzi, D., Shen, X., DiGiuseppe, J. A., Taylor, H., Hermankova, M., Chadwick, K., Margolick, J., Quinn, T. C., Kuo, Y. H., Brookmeyer, R., Zeiger, M. A., Barditch-Crovo, P. & Siliciano, R. F. (1997). Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection.Nature 387, 183-187.[CrossRef] [Google Scholar]
  4. Copeland, K. F. T., McKay, P. J. & Rosenthal, K. L. (1995). Suppression of activation of the human immunodeficiency virus long terminal repeat by CD8+ T cells is not lentivirus specific.AIDS Research and Human Retroviruses 11, 1321-1326.[CrossRef] [Google Scholar]
  5. Higashikubo, R., Wright, W. D. & Roti, J. L. (1990). Flow cytometric methods for studying isolated nuclei. In Flow Cytometry. Edited by Z. Darzynkiewcz & H. Crissman. New York: Academic Press.
  6. Kasama, T., Strieter, R. M., Lukacs, N. W., Burdick, M. D. & Kunkel, S. L. (1994). Regulation of neutrophil-derived chemokine expression by IL-10.Journal of Immunology 152, 3559-3569. [Google Scholar]
  7. Levy, J. A., Mackewicz, C. E. & Barker, E. (1996). Controlling HIV pathogenesis: the role of noncytotoxic anti-HIV activity of CD8+ cells.Immunology Today 17, 217-224.[CrossRef] [Google Scholar]
  8. Mackewicz, C. & Levy, J. A. (1992). CD8+ cell anti-HIV activity: nonlytic suppression of virus replication.AIDS Research and Human Retroviruses 8, 1039-1050.[CrossRef] [Google Scholar]
  9. Mackewicz, C. E., Ortega, H. & Levy, J. A. (1994). Effect of cytokines on HIV replication in CD4+ lymphocytes: lack of identity with the CD8+ cell antiviral factor.Cellular Immunology 153, 329-343.[CrossRef] [Google Scholar]
  10. Mackewicz, C. E., Blackbourn, D. J. & Levy, J. A. (1995). CD8+ cells suppress human immunodeficiency virus replication by inhibiting viral transcription.Proceedings of the National Academy of Sciences, USA 92, 2308-2312.[CrossRef] [Google Scholar]
  11. Patterson, B. K., Till, M., Otto, P., Goolsby, C., Furtado, M. R., McBride, L. J. & Wolinsky, S. M. (1993). Detection of HIV-1 DNA and messenger RNA in individual cells by PCR-driven in situ hybridization and flow cytometry.Science 260, 976-979.[CrossRef] [Google Scholar]
  12. Patterson, B. K., Jiyamapa, D., Mayrand, E., Hoff, B., Abramson, R. & Garcia, P. M. (1996). Detection of HIV-1 DNA in cells and tissue by fluorescent in situ 5′-nuclease assay (FISNA).Nucleic Acids Research 24, 3656-3658.[CrossRef] [Google Scholar]
  13. Patterson, B. K., Landay, A., Andersson, J., Brown, C., Behbahani, H., Jiyamapa, D., Burki, Z., Stanislawski, D., Czerniewski, M. A. & Garcia, P. (1998). Repertoire of chemokine receptor expression in the female genital tract: implications for human immunodeficiency virus transmission.American Journal of Pathology 153, 481-490.[CrossRef] [Google Scholar]
  14. Patterson, B. K., Czerniewski, M., Andersson, J., Sullivan, Y., Su, F., Jiyamapa, D., Burki, Z. & Landay, A. (1999). Regulation of CCR5 and CXCR4 expression by type 1 and type 2 cytokines: CCR5 expression is downregulated by IL-10 in CD4-positive lymphocytes.Clinical Immunology 91, 254-262.[CrossRef] [Google Scholar]
  15. Sanchez-Pescador, R., Power, M. D., Barr, P. J., Steimer, K. S., Stempien, M. M., Brown-Shimer, S. L., Gee, W. W., Renard, A., Randolph, A., Levy, J. A., Dina, D. & Luciw, P. A. (1985). Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2).Science 227, 484-492.[CrossRef] [Google Scholar]
  16. Sato, A., Mackewicz, C. E., Gaynor, R. H. & Levy, J. A. (1996). CD8+ T cell culture fluids from HIV infected individuals suppress HIV-1 long terminal repeat (LTR) driven transcription. In XI International AIDS Conference, p. 211. Vancouver, BC, Canada.
  17. Tang, S., Patterson, B. & Levy, J. A. (1995). Highly purified quiescent human peripheral blood CD4+ T cells are infectible by human immunodeficiency virus but do not release virus after activation.Journal of Virology 69, 5659-5665. [Google Scholar]
  18. Walker, C. M., Moody, D. J., Stites, D. P. & Levy, J. A. (1986). CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication.Science 234, 1563-1566.[CrossRef] [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-81-5-1261
Loading
/content/journal/jgv/10.1099/0022-1317-81-5-1261
Loading

Data & Media loading...

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