A selective defect of interferon a production in human immunodeficiency virus-infected monocytes

Howard Eliot Gendelman, Robert M. Friedman, Steve Joe, Lisa M. Baca, Jim A. Turpin, Gabriela Dveksler, Monte S. Meltzer, Carl Dieffenbach

Research output: Contribution to journalArticle

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Abstract

Interferon α (IFN-α) induces significant antiretroviral activities that affect the ability of human immunodeficiency virus (HIV) to infect and replicate in its principal target cells, CD4+ T cells and macrophages. A major endogenous source of IFN-a during any infection is the macrophage. Thus, macrophages have the potential to produce both IFN-α and HIV. In this study, we examined the production of IFN-α and other cytokines by macrophage colony-stimulating factor (M-CSF)- treated cultured monorytes during HIV infection. Tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), IL-6, IFN-ω, or IFN-β were not detected nor was the mRNA expressed in either uninfected or HIVinfected monorytes. However, both uninfected and HIVinfected monorytes produced high levels of each of these cytokines after treatment with synthetic double-stranded RNA [poly(I)-poly(C)]. Uninfected monorytes also produced high levels of IFN-α after treatment with poly(I)-poly(C), Newcastle disease virus, or herpes simplex virus. In marked contrast to the preceding observations, HIVinfected monorytes produced little or no IFN-α before or after treatment with any of these agents. The absence of detectable IFN-α activity and mRNA in poly(I).poly(C)-treated HIV-infected monorytes was coincident with high levels of 2’,5’ oligoadenylate synthetase and complete ablation of HIV gene expression. The antiviral activity induced by poly(I)-poly(C) may be a direct effect of this synthetic doubled-stranded RNA or secondary to the low levels of IFN-β and IFN-ω produced by infected cells. The markedly diminished capacity of HIV-infected monorytes to produce IFN-oc may reflect a specific adaptive mechanism ofvirus to alter basic microbicidal functions of this cell. The inevitable result of this HIV-induced cytokine dysregulation is virus replication and persistence in mononuclear phagocytes.

Original languageEnglish (US)
Pages (from-to)1433-1442
Number of pages10
JournalJournal of Experimental Medicine
Volume172
Issue number5
DOIs
StatePublished - Nov 1 1990

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Interferons
Monocytes
Poly C
HIV
Poly I-C
Macrophages
Cytokines
Poly I
Newcastle disease virus
Messenger RNA
Macrophage Colony-Stimulating Factor
Double-Stranded RNA
Virus Diseases
Simplexvirus
Phagocytes
Ligases
Virus Replication
Interleukin-1
Antiviral Agents
Interleukin-6

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

A selective defect of interferon a production in human immunodeficiency virus-infected monocytes. / Gendelman, Howard Eliot; Friedman, Robert M.; Joe, Steve; Baca, Lisa M.; Turpin, Jim A.; Dveksler, Gabriela; Meltzer, Monte S.; Dieffenbach, Carl.

In: Journal of Experimental Medicine, Vol. 172, No. 5, 01.11.1990, p. 1433-1442.

Research output: Contribution to journalArticle

Gendelman, HE, Friedman, RM, Joe, S, Baca, LM, Turpin, JA, Dveksler, G, Meltzer, MS & Dieffenbach, C 1990, 'A selective defect of interferon a production in human immunodeficiency virus-infected monocytes', Journal of Experimental Medicine, vol. 172, no. 5, pp. 1433-1442. https://doi.org/10.1084/jem.172.5.1433
Gendelman, Howard Eliot ; Friedman, Robert M. ; Joe, Steve ; Baca, Lisa M. ; Turpin, Jim A. ; Dveksler, Gabriela ; Meltzer, Monte S. ; Dieffenbach, Carl. / A selective defect of interferon a production in human immunodeficiency virus-infected monocytes. In: Journal of Experimental Medicine. 1990 ; Vol. 172, No. 5. pp. 1433-1442.
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AU - Meltzer, Monte S.

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