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

Rachel D. Schwer, J. Allan McCutchan, J. Clark Venable, Jay Nelson, Clayton A. Wiley

Research output: Contribution to journalArticle

37 Citations (Scopus)

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-aetivated, 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.

Original languageEnglish (US)
Pages (from-to)3280-3288
Number of pages9
JournalJournal of Virology
Volume64
Issue number7
StatePublished - 1990
Externally publishedYes

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Human immunodeficiency virus
macrophages
T-lymphocytes
Macrophages
HIV
T-Lymphocytes
monocytes
Monocytes
cells
infection
Lentivirus Infections
Infection
Tissue Donors
Antigens
antigens
HIV-2
Lentivirus
Virus Replication
Concanavalin A
Coculture Techniques

ASJC Scopus subject areas

  • Immunology

Cite this

Schwer, R. D., Allan McCutchan, J., Clark Venable, J., Nelson, J., & Wiley, C. A. (1990). T-cell-induced expression of human immunodeficiency virus in macrophages. Journal of Virology, 64(7), 3280-3288.

T-cell-induced expression of human immunodeficiency virus in macrophages. / Schwer, Rachel D.; Allan McCutchan, J.; Clark Venable, J.; Nelson, Jay; Wiley, Clayton A.

In: Journal of Virology, Vol. 64, No. 7, 1990, p. 3280-3288.

Research output: Contribution to journalArticle

Schwer, RD, Allan McCutchan, J, Clark Venable, J, Nelson, J & Wiley, CA 1990, 'T-cell-induced expression of human immunodeficiency virus in macrophages', Journal of Virology, vol. 64, no. 7, pp. 3280-3288.
Schwer RD, Allan McCutchan J, Clark Venable J, Nelson J, Wiley CA. T-cell-induced expression of human immunodeficiency virus in macrophages. Journal of Virology. 1990;64(7):3280-3288.
Schwer, Rachel D. ; Allan McCutchan, J. ; Clark Venable, J. ; Nelson, Jay ; Wiley, Clayton A. / T-cell-induced expression of human immunodeficiency virus in macrophages. In: Journal of Virology. 1990 ; Vol. 64, No. 7. pp. 3280-3288.
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