Regulation of cytokine and viral gene expression in monocytes infected with the human immunodeficiency virus

M. S. Meltzer, L. Baca, J. A. Turpin, D. C. Kalter, C. Dieffenbach, R. M. Friedman, H. E. Gendelman

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Monocytes treated with interferon-α (IFN-α) at virus challenge show no evidence of human immunodeficiency virus (HIV) infection: no p24 antigen or reverse transcriptase (RT) activity, no viral mRNA and no proviral DNA. Levels of p24 antigen and RT activity in monocytes infected with HIV 1-3 weeks before IFN-α treatment gradually decrease to baseline. HIV-induced cytopathic changes are markedly reduced, as are levels of HIV mRNA: the frequency of productively infected cells is ≤1%. But, levels of proviral DNA in the IFN-α-treated and control HIV-infected cells are indistinguishable, and remain so through 3 weeks. Large quantities of proviral DNA in IFN-α-treated cells with little active transcription suggest true microbiological latency. The major potential source for IFN-α in HIV-infected patients is the macrophage. With any of 15 virus isolates, tumor necrosis factor-α, interleukin-1β, interleukin-6, IFN-ω or IFN-β are not detected nor the mRNA expressed in HIV-infected or uninfected monocytes. Both uninfected and HIV-infected monocytes produce high levels of these cytokines after treatment with synthetic double-stranded RNA (poly-I:C). Uninfected monocytes also produce high levels of IFN-α after treatment with Poly-I:C, Newcastle disease virus or herpes simplex virus. In marked contrast, HIV-infected monocytes express no IFN-α activity or mRNA before or after treatment with any of these agents. The markedly diminished capacity of HIV-infected monocyte to produce IFN-α reflects a specific transcriptional block and may be an adaptive mechanism of virus 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)209-213
Number of pages5
JournalPathobiology
Volume59
Issue number4
DOIs
StatePublished - 1991

Keywords

  • cytokines
  • human immunodeficiency virus
  • interferon
  • monocytes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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    Meltzer, M. S., Baca, L., Turpin, J. A., Kalter, D. C., Dieffenbach, C., Friedman, R. M., & Gendelman, H. E. (1991). Regulation of cytokine and viral gene expression in monocytes infected with the human immunodeficiency virus. Pathobiology, 59(4), 209-213. https://doi.org/10.1159/000163647