Regulation of HIV replication in infected monocytes by IFN-α: Mechanisms for viral restriction

H. E. Gendelman, L. M. Baca, J. Turpin, D. C. Kalter, B. Hansen, J. M. Orenstein, C. W. Dieffenbach, R. M. Friedman, M. S. Meltzer

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115 Scopus citations

Abstract

In a survey of 15 different virus isolates, no IFN-α or IFN-β activity was detected in culture fluids of HIV-infected T cells or monocytes. Exogenous rIFN-α added to T lymphoblast or monocyte cultures induced restriction in replication of the amphotropic HIV that infect both cell types. With IFN-treated HIV-infected T cells, levels of reverse transcriptase (RT) activity in culture fluids were half those in control cultures, but the frequency of infected cells or the levels of p24 Ag released in culture fluids were unchanged. In contrast to the modest effect of IFN on HIV-infected T cells, IFN-induced antiviral activity in monocytes was quite dramatic. Monocytes treated with IFN at the time of virus challenge showed no evidence of HIV infection: no p24 Ag or RT activity, no viral mRNA, and no proviral DNA. In this system, IFN interrupts one or more early event(s) in the virus replication cycle before formation of proviral DNA. Monocyte cultures infected with HIV 7 days before IFN treatment showed a gradual decrease in levels of p24 Ag and RT activity to baseline by 3 wk. HIV-induced cytopathic changes were markedly reduced, and the frequency of productively infected cells was ≤1% of total cells. Virus particles released 24 h after IFN treatment were 100- to 1000-fold less infectious than equal numbers of control virions. But, monocytes treated with IFN 7 days after HIV infection were not free of the retroviral pathogen: levels of proviral DNA in the IFN-treated and control HIV-infected cells were indistinguishable. The presence of large quantities of proviral DNA in cells with little or no evidence for active transcription documents a situation approaching true microbiological latency.

Original languageEnglish (US)
Pages (from-to)2669-2676
Number of pages8
JournalJournal of Immunology
Volume145
Issue number8
StatePublished - Jan 1 1990

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Gendelman, H. E., Baca, L. M., Turpin, J., Kalter, D. C., Hansen, B., Orenstein, J. M., Dieffenbach, C. W., Friedman, R. M., & Meltzer, M. S. (1990). Regulation of HIV replication in infected monocytes by IFN-α: Mechanisms for viral restriction. Journal of Immunology, 145(8), 2669-2676.