Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1991 Apr;65(4):2019–2023. doi: 10.1128/jvi.65.4.2019-2023.1991

Few infected CD4+ T cells but a high proportion of replication-competent provirus copies in asymptomatic human immunodeficiency virus type 1 infection.

J E Brinchmann 1, J Albert 1, F Vartdal 1
PMCID: PMC240046  PMID: 1672165

Abstract

The virus load in CD4+ T cells from six asymptomatic human immunodeficiency virus type 1 (HIV-1)-infected individuals was determined by limiting-dilution analysis with a sensitive virus isolation procedure and the polymerase chain reaction (PCR). Both methods allowed detection of one HIV-1-infected cell among 10(5) uninfected cells. The number of provirus-containing CD4+ T cells was found to be 1 per 4,000 to 150,000 (median, 1 per 29,000), as determined by virus isolation and 1 per 2,500 to 26,000 (median, 1 per 12,000), as determined by PCR. Infected cells contained an average of 1 to 2 provirus copies, and a high proportion of the provirus copies (1 in 1 to 1 in 6; median, 1 in 2) were replication competent. The results suggest that only a few CD4+ T cells are likely to be lost as a direct consequence of the presence of HIV-1 in infected cells in asymptomatic individuals and that additional mechanisms may contribute to the depletion of CD4+ T cells observed in vivo.

Full text

PDF
2019

Images in this article

2021Image
on p.2021

Selected References

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

  1. Albert J., Fenyö E. M. Simple, sensitive, and specific detection of human immunodeficiency virus type 1 in clinical specimens by polymerase chain reaction with nested primers. J Clin Microbiol. 1990 Jul;28(7):1560–1564. doi: 10.1128/jcm.28.7.1560-1564.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brinchmann J. E., Gaudernack G., Thorsby E., Jonassen T. O., Vartdal F. Reliable isolation of human immunodeficiency virus from cultures of naturally infected CD4+ T cells. J Virol Methods. 1989 Sep;25(3):293–300. doi: 10.1016/0166-0934(89)90056-6. [DOI] [PubMed] [Google Scholar]
  3. Brinchmann J. E., Vartdal F., Gaudernack G., Markussen G., Funderud S., Ugelstad J., Thorsby E. Direct immunomagnetic quantification of lymphocyte subsets in blood. Clin Exp Immunol. 1988 Jan;71(1):182–186. [PMC free article] [PubMed] [Google Scholar]
  4. Brinchmann J. E., Vartdal F., Thorsby E. T lymphocyte subset changes in human immunodeficiency virus infection. J Acquir Immune Defic Syndr. 1989;2(4):398–403. [PubMed] [Google Scholar]
  5. Clouse K. A., Powell D., Washington I., Poli G., Strebel K., Farrar W., Barstad P., Kovacs J., Fauci A. S., Folks T. M. Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone. J Immunol. 1989 Jan 15;142(2):431–438. [PubMed] [Google Scholar]
  6. Folks T. M., Kessler S. W., Orenstein J. M., Justement J. S., Jaffe E. S., Fauci A. S. Infection and replication of HIV-1 in purified progenitor cells of normal human bone marrow. Science. 1988 Nov 11;242(4880):919–922. doi: 10.1126/science.2460922. [DOI] [PubMed] [Google Scholar]
  7. Harper M. E., Marselle L. M., Gallo R. C., Wong-Staal F. Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proc Natl Acad Sci U S A. 1986 Feb;83(3):772–776. doi: 10.1073/pnas.83.3.772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ho D. D., Moudgil T., Alam M. Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N Engl J Med. 1989 Dec 14;321(24):1621–1625. doi: 10.1056/NEJM198912143212401. [DOI] [PubMed] [Google Scholar]
  9. Huet T., Dazza M. C., Brun-Vézinet F., Roelants G. E., Wain-Hobson S. A highly defective HIV-1 strain isolated from a healthy Gabonese individual presenting an atypical western blot. AIDS. 1989 Nov;3(11):707–715. doi: 10.1097/00002030-198911000-00004. [DOI] [PubMed] [Google Scholar]
  10. Kim S. Y., Byrn R., Groopman J., Baltimore D. Temporal aspects of DNA and RNA synthesis during human immunodeficiency virus infection: evidence for differential gene expression. J Virol. 1989 Sep;63(9):3708–3713. doi: 10.1128/jvi.63.9.3708-3713.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Meyerhans A., Cheynier R., Albert J., Seth M., Kwok S., Sninsky J., Morfeldt-Månson L., Asjö B., Wain-Hobson S. Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations. Cell. 1989 Sep 8;58(5):901–910. doi: 10.1016/0092-8674(89)90942-2. [DOI] [PubMed] [Google Scholar]
  12. Pauza C. D., Galindo J. E., Richman D. D. Reinfection results in accumulation of unintegrated viral DNA in cytopathic and persistent human immunodeficiency virus type 1 infection of CEM cells. J Exp Med. 1990 Oct 1;172(4):1035–1042. doi: 10.1084/jem.172.4.1035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Poli G., Orenstein J. M., Kinter A., Folks T. M., Fauci A. S. Interferon-alpha but not AZT suppresses HIV expression in chronically infected cell lines. Science. 1989 May 5;244(4904):575–577. doi: 10.1126/science.2470148. [DOI] [PubMed] [Google Scholar]
  14. Psallidopoulos M. C., Schnittman S. M., Thompson L. M., 3rd, Baseler M., Fauci A. S., Lane H. C., Salzman N. P. Integrated proviral human immunodeficiency virus type 1 is present in CD4+ peripheral blood lymphocytes in healthy seropositive individuals. J Virol. 1989 Nov;63(11):4626–4631. doi: 10.1128/jvi.63.11.4626-4631.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Robinson H. L., Zinkus D. M. Accumulation of human immunodeficiency virus type 1 DNA in T cells: results of multiple infection events. J Virol. 1990 Oct;64(10):4836–4841. doi: 10.1128/jvi.64.10.4836-4841.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rosenberg Z. F., Fauci A. S. The immunopathogenesis of HIV infection. Adv Immunol. 1989;47:377–431. doi: 10.1016/s0065-2776(08)60665-3. [DOI] [PubMed] [Google Scholar]
  17. Schnittman S. M., Denning S. M., Greenhouse J. J., Justement J. S., Baseler M., Kurtzberg J., Haynes B. F., Fauci A. S. Evidence for susceptibility of intrathymic T-cell precursors and their progeny carrying T-cell antigen receptor phenotypes TCR alpha beta + and TCR gamma delta + to human immunodeficiency virus infection: a mechanism for CD4+ (T4) lymphocyte depletion. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7727–7731. doi: 10.1073/pnas.87.19.7727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Schnittman S. M., Psallidopoulos M. C., Lane H. C., Thompson L., Baseler M., Massari F., Fox C. H., Salzman N. P., Fauci A. S. The reservoir for HIV-1 in human peripheral blood is a T cell that maintains expression of CD4. Science. 1989 Jul 21;245(4915):305–308. doi: 10.1126/science.2665081. [DOI] [PubMed] [Google Scholar]
  19. Shibata D., Brynes R. K., Nathwani B., Kwok S., Sninsky J., Arnheim N. Human immunodeficiency viral DNA is readily found in lymph node biopsies from seropositive individuals. Analysis of fixed tissue using the polymerase chain reaction. Am J Pathol. 1989 Oct;135(4):697–702. [PMC free article] [PubMed] [Google Scholar]
  20. Simmonds P., Balfe P., Peutherer J. F., Ludlam C. A., Bishop J. O., Brown A. J. Human immunodeficiency virus-infected individuals contain provirus in small numbers of peripheral mononuclear cells and at low copy numbers. J Virol. 1990 Feb;64(2):864–872. doi: 10.1128/jvi.64.2.864-872.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Temin H. M. Mechanisms of cell killing/cytopathic effects by nonhuman retroviruses. Rev Infect Dis. 1988 Mar-Apr;10(2):399–405. doi: 10.1093/clinids/10.2.399. [DOI] [PubMed] [Google Scholar]
  22. 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]

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

RESOURCES