Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1990 Jul;64(7):3280–3288. doi: 10.1128/jvi.64.7.3280-3288.1990

T-cell-induced expression of human immunodeficiency virus in macrophages.

R D Schrier 1, J A McCutchan 1, J C Venable 1, J A Nelson 1, C A Wiley 1
PMCID: PMC249555  PMID: 2112615

Abstract

Macrophages are major reservoirs of human immunodeficiency virus (HIV) in the tissues of infected humans. As monocytes in the peripheral blood do not show high levels of infection, we have investigated the expression of HIV in T-cell-activated, differentiated macrophages. Peripheral blood mononuclear cells were isolated from HIV-seropositive individuals and stimulated with antigens or mitogens, and the nonadherent fraction was removed. Macrophages were cultured alone for 2 weeks, and HIV expression was assessed. Results from p24 antigen capture assays demonstrated that the presence of autologous T cells and concanavalin A or autologous T cells and allogeneic cells for the initial 24 h of culture induced HIV expression in 35 of 47 (74%) HIV-seropositive patients tested. The macrophage monolayers could be immunostained with anti-HIV antibodies to reveal discrete infectious centers, indicating that complete virus replication was occurring in the macrophages and that infection of adjacent cells was mediated by cell-cell contact. Time course studies of the interval of coculture of the adherent and nonadherent cells indicated that 24 h (but not 2 h) was sufficient for induction of HIV in the macrophages. Direct contact between the adherent cells and activated T cells was required as well. Since the presence of autologous T cells also appeared to be necessary, induction of HIV expression in macrophages may be genetically restricted. HIV-seronegative nonadherent cells were able to induce HIV expression in macrophages from HIV-seropositive donors, demonstrating that the virus originated in the monocytes and was reactivated in the context of a classic T-cell-mediated immune reaction. The high percentage of monocytes from HIV-seropositive donors which can be induced to replicate HIV by activated T cells suggests that infection of monocytes may be critical to the pathogenesis of this lentivirus infection.

Full text

PDF
3280

Images in this article

3284Image
on p.3284

Selected References

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

  1. Becker J., Ulrich P., Kunze R., Gelderblom H., Langford A., Reichart P. Immunohistochemical detection of HIV structural proteins and distribution of T-lymphocytes and Langerhans cells in the oral mucosa of HIV infected patients. Virchows Arch A Pathol Anat Histopathol. 1988;412(5):413–419. doi: 10.1007/BF00750575. [DOI] [PubMed] [Google Scholar]
  2. Collman R., Hassan N. F., Walker R., Godfrey B., Cutilli J., Hastings J. C., Friedman H., Douglas S. D., Nathanson N. Infection of monocyte-derived macrophages with human immunodeficiency virus type 1 (HIV-1). Monocyte-tropic and lymphocyte-tropic strains of HIV-1 show distinctive patterns of replication in a panel of cell types. J Exp Med. 1989 Oct 1;170(4):1149–1163. doi: 10.1084/jem.170.4.1149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Crowe S., Mills J., McGrath M. S. Quantitative immunocytofluorographic analysis of CD4 surface antigen expression and HIV infection of human peripheral blood monocyte/macrophages. AIDS Res Hum Retroviruses. 1987 Summer;3(2):135–145. doi: 10.1089/aid.1987.3.135. [DOI] [PubMed] [Google Scholar]
  4. Gartner S., Markovits P., Markovitz D. M., Betts R. F., Popovic M. Virus isolation from and identification of HTLV-III/LAV-producing cells in brain tissue from a patient with AIDS. JAMA. 1986 Nov 7;256(17):2365–2371. [PubMed] [Google Scholar]
  5. Gartner S., Markovits P., Markovitz D. M., Kaplan M. H., Gallo R. C., Popovic M. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science. 1986 Jul 11;233(4760):215–219. doi: 10.1126/science.3014648. [DOI] [PubMed] [Google Scholar]
  6. Gendelman H. E., Orenstein J. M., Baca L. M., Weiser B., Burger H., Kalter D. C., Meltzer M. S. The macrophage in the persistence and pathogenesis of HIV infection. AIDS. 1989 Aug;3(8):475–495. doi: 10.1097/00002030-198908000-00001. [DOI] [PubMed] [Google Scholar]
  7. Gendelman H. E., Orenstein J. M., Martin M. A., Ferrua C., Mitra R., Phipps T., Wahl L. A., Lane H. C., Fauci A. S., Burke D. S. Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor 1-treated monocytes. J Exp Med. 1988 Apr 1;167(4):1428–1441. doi: 10.1084/jem.167.4.1428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hirsch M. S., Phillips S. M., Solnik C., Black P. H., Schwartz R. S., Carpenter C. B. Activation of leukemia viruses by graft-versus-host and mixed lymphocyte reactions in vitro. Proc Natl Acad Sci U S A. 1972 May;69(5):1069–1072. doi: 10.1073/pnas.69.5.1069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ho D. D., Rota T. R., Schooley R. T., Kaplan J. C., Allan J. D., Groopman J. E., Resnick L., Felsenstein D., Andrews C. A., Hirsch M. S. Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N Engl J Med. 1985 Dec 12;313(24):1493–1497. doi: 10.1056/NEJM198512123132401. [DOI] [PubMed] [Google Scholar]
  10. Koenig S., Gendelman H. E., Orenstein J. M., Dal Canto M. C., Pezeshkpour G. H., Yungbluth M., Janotta F., Aksamit A., Martin M. A., Fauci A. S. Detection of AIDS virus in macrophages in brain tissue from AIDS patients with encephalopathy. Science. 1986 Sep 5;233(4768):1089–1093. doi: 10.1126/science.3016903. [DOI] [PubMed] [Google Scholar]
  11. Kornbluth R. S., Oh P. S., Munis J. R., Cleveland P. H., Richman D. D. Interferons and bacterial lipopolysaccharide protect macrophages from productive infection by human immunodeficiency virus in vitro. J Exp Med. 1989 Mar 1;169(3):1137–1151. doi: 10.1084/jem.169.3.1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kreipe H., Radzun H. J., Rudolph P., Barth J., Hansmann M. L., Heidorn K., Parwaresch M. R. Multinucleated giant cells generated in vitro. Terminally differentiated macrophages with down-regulated c-fms expression. Am J Pathol. 1988 Feb;130(2):232–243. [PMC free article] [PubMed] [Google Scholar]
  13. Le Tourneau A., Audouin J., Diebold J., Marche C., Tricottet V., Reynes M. LAV-like viral particles in lymph node germinal centers in patients with the persistent lymphadenopathy syndrome and the acquired immunodeficiency syndrome-related complex: an ultrastructural study of 30 cases. Hum Pathol. 1986 Oct;17(10):1047–1053. doi: 10.1016/s0046-8177(86)80089-2. [DOI] [PubMed] [Google Scholar]
  14. McElrath M. J., Pruett J. E., Cohn Z. A. Mononuclear phagocytes of blood and bone marrow: comparative roles as viral reservoirs in human immunodeficiency virus type 1 infections. Proc Natl Acad Sci U S A. 1989 Jan;86(2):675–679. doi: 10.1073/pnas.86.2.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mizel S. B. The interleukins. FASEB J. 1989 Oct;3(12):2379–2388. doi: 10.1096/fasebj.3.12.2676681. [DOI] [PubMed] [Google Scholar]
  16. Murray H. W. Macrophage activation in the acquired immunodeficiency syndrome. Adv Exp Med Biol. 1988;239:297–307. doi: 10.1007/978-1-4757-5421-6_30. [DOI] [PubMed] [Google Scholar]
  17. Murray H. W., Scavuzzo D., Jacobs J. L., Kaplan M. H., Libby D. M., Schindler J., Roberts R. B. In vitro and in vivo activation of human mononuclear phagocytes by interferon-gamma. Studies with normal and AIDS monocytes. J Immunol. 1987 Apr 15;138(8):2457–2462. [PubMed] [Google Scholar]
  18. Nathan C. F., Murray H. W., Wiebe M. E., Rubin B. Y. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med. 1983 Sep 1;158(3):670–689. doi: 10.1084/jem.158.3.670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nathan C. F. Secretory products of macrophages. J Clin Invest. 1987 Feb;79(2):319–326. doi: 10.1172/JCI112815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nicholson J. K., Cross G. D., Callaway C. S., McDougal J. S. In vitro infection of human monocytes with human T lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). J Immunol. 1986 Jul 1;137(1):323–329. [PubMed] [Google Scholar]
  21. Olding L. B., Jensen F. C., Oldstone M. B. Pathogenesis of of cytomegalovirus infection. I. Activation of virus from bone marrow-derived lymphocytes by in vitro allogenic reaction. J Exp Med. 1975 Mar 1;141(3):561–572. doi: 10.1084/jem.141.3.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Perno C. F., Yarchoan R., Cooney D. A., Hartman N. R., Gartner S., Popovic M., Hao Z., Gerrard T. L., Wilson Y. A., Johns D. G. Inhibition of human immunodeficiency virus (HIV-1/HTLV-IIIBa-L) replication in fresh and cultured human peripheral blood monocytes/macrophages by azidothymidine and related 2',3'-dideoxynucleosides. J Exp Med. 1988 Sep 1;168(3):1111–1125. doi: 10.1084/jem.168.3.1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Poli G., Bottazzi B., Acero R., Bersani L., Rossi V., Introna M., Lazzarin A., Galli M., Mantovani A. Monocyte function in intravenous drug abusers with lymphadenopathy syndrome and in patients with acquired immunodeficiency syndrome: selective impairment of chemotaxis. Clin Exp Immunol. 1985 Oct;62(1):136–142. [PMC free article] [PubMed] [Google Scholar]
  24. Pumarola-Sune T., Navia B. A., Cordon-Cardo C., Cho E. S., Price R. W. HIV antigen in the brains of patients with the AIDS dementia complex. Ann Neurol. 1987 May;21(5):490–496. doi: 10.1002/ana.410210513. [DOI] [PubMed] [Google Scholar]
  25. Rappersberger K., Gartner S., Schenk P., Stingl G., Groh V., Tschachler E., Mann D. L., Wolff K., Konrad K., Popovic M. Langerhans' cells are an actual site of HIV-1 replication. Intervirology. 1988;29(4):185–194. doi: 10.1159/000150045. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Schrier R. D., Gnann J. W., Jr, Landes R., Lockshin C., Richman D., McCutchan A., Kennedy C., Oldstone M. B., Nelson J. A. T cell recognition of HIV synthetic peptides in a natural infection. J Immunol. 1989 Feb 15;142(4):1166–1176. [PubMed] [Google Scholar]
  28. Smith P. D., Ohura K., Masur H., Lane H. C., Fauci A. S., Wahl S. M. Monocyte function in the acquired immune deficiency syndrome. Defective chemotaxis. J Clin Invest. 1984 Dec;74(6):2121–2128. doi: 10.1172/JCI111637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Tschachler E., Groh V., Popovic M., Mann D. L., Konrad K., Safai B., Eron L., diMarzo Veronese F., Wolff K., Stingl G. Epidermal Langerhans cells--a target for HTLV-III/LAV infection. J Invest Dermatol. 1987 Feb;88(2):233–237. doi: 10.1111/1523-1747.ep12525402. [DOI] [PubMed] [Google Scholar]
  31. Wahl L. M., Corcoran M. L., Pyle S. W., Arthur L. O., Harel-Bellan A., Farrar W. L. Human immunodeficiency virus glycoprotein (gp120) induction of monocyte arachidonic acid metabolites and interleukin 1. Proc Natl Acad Sci U S A. 1989 Jan;86(2):621–625. doi: 10.1073/pnas.86.2.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wahl S. M., Allen J. B., Gartner S., Orenstein J. M., Popovic M., Chenoweth D. E., Arthur L. O., Farrar W. L., Wahl L. M. HIV-1 and its envelope glycoprotein down-regulate chemotactic ligand receptors and chemotactic function of peripheral blood monocytes. J Immunol. 1989 May 15;142(10):3553–3559. [PubMed] [Google Scholar]
  33. Wiley C. A., Schrier R. D., Nelson J. A., Lampert P. W., Oldstone M. B. Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7089–7093. doi: 10.1073/pnas.83.18.7089. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES