Induction of IFN-α in peripheral blood mononuclear cells by HIV-infected monocytes: Restricted antiviral activity of the HIV-induced IFN

Howard E. Gendelman, Lisa M. Baca, Corinne A. Kubrak, Peter Genis, Sarah Burrous, Robert M. Friedman, Dana Jacobs, Monte S. Meltzer

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Abstract

PBMC cocultured with HIV-infected monocytes for 12 to 48 h released high levels of IFN activity. IFN titers were directly dependent upon time after virus infection and level of HIV replication in infected cells. IFN induction in PBMC was evident with HIV-infected monocytes and PBMC and with myeloid and lymphoblastoid cell lines with at least three different HIV strains. In HIV-infected cell line pairs in which virus infection occurs in both productive and restricted forms, IFN induction in PBMC occurred only with productive infection. IFN activity was acid stable and completely neutralized by antibodies against IFN-α. Induction of IFN required cell-cell contact between HIV-infected cells and PBMC, but was independent of MHC compatibility. With PBMC cocultured with autologous HIV-infected monocytes, IFN induction was highly selective: IL-1β, IL-6, or TNF-α activity and mRNA were not detected. Cell surface determinants on HIV-infected monocytes that induced IFN in PBMC remained active after fixation in 4% paraformaldehye. Both adherent and nonadherent PBMC produced IFN after coculture with HTV-infected monocytes. Ability to produce IFN by PBMC was not affected by depletion of T cell, NK cell, B cell, or monocyte subpopulations. The IFN activity produced by PBMC cocultured with HIV-infected cells was about 20-fold less active than equal quantities of rIFN-α2b for inhibition of HIV replication in monocytes and at low concentrations enhanced virus growth. Clinical studies with HIV-infected patients and parallel findings in animal lentivirus disease suggest an adverse role for IFN in disease progression. Conditions for induction of IFN in the culture system described in this report may mimic those in the HIV-infected patient. Defining the molecular basis for IFN induction, the cells that produce IFN, and the altered biologic activity of this important cytokine may provide insight into the pathogenesis of HIV disease.

Original languageEnglish (US)
Pages (from-to)422-429
Number of pages8
JournalJournal of Immunology
Volume148
Issue number2
StatePublished - Jan 15 1992

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Antiviral Agents
Monocytes
Blood Cells
HIV
Virus Diseases
Cell Line
Lentivirus
Animal Diseases
Myeloid Cells
Coculture Techniques
Interleukin-1
Natural Killer Cells
Disease Progression
Interleukin-6
B-Lymphocytes
Cytokines
Viruses
T-Lymphocytes
Messenger RNA
Acids

ASJC Scopus subject areas

  • Immunology

Cite this

Gendelman, H. E., Baca, L. M., Kubrak, C. A., Genis, P., Burrous, S., Friedman, R. M., ... Meltzer, M. S. (1992). Induction of IFN-α in peripheral blood mononuclear cells by HIV-infected monocytes: Restricted antiviral activity of the HIV-induced IFN. Journal of Immunology, 148(2), 422-429.

Induction of IFN-α in peripheral blood mononuclear cells by HIV-infected monocytes : Restricted antiviral activity of the HIV-induced IFN. / Gendelman, Howard E.; Baca, Lisa M.; Kubrak, Corinne A.; Genis, Peter; Burrous, Sarah; Friedman, Robert M.; Jacobs, Dana; Meltzer, Monte S.

In: Journal of Immunology, Vol. 148, No. 2, 15.01.1992, p. 422-429.

Research output: Contribution to journalArticle

Gendelman, HE, Baca, LM, Kubrak, CA, Genis, P, Burrous, S, Friedman, RM, Jacobs, D & Meltzer, MS 1992, 'Induction of IFN-α in peripheral blood mononuclear cells by HIV-infected monocytes: Restricted antiviral activity of the HIV-induced IFN', Journal of Immunology, vol. 148, no. 2, pp. 422-429.
Gendelman, Howard E. ; Baca, Lisa M. ; Kubrak, Corinne A. ; Genis, Peter ; Burrous, Sarah ; Friedman, Robert M. ; Jacobs, Dana ; Meltzer, Monte S. / Induction of IFN-α in peripheral blood mononuclear cells by HIV-infected monocytes : Restricted antiviral activity of the HIV-induced IFN. In: Journal of Immunology. 1992 ; Vol. 148, No. 2. pp. 422-429.
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