Regulation of cytokine and viral gene expression in monocytes infected with the human immunodeficiency virus.
Monocytes treated with interferon-alpha (IFN-alpha) 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-alpha 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 less than or equal to 1%. But, levels of proviral DNA in the IFN-alpha-treated and control HIV-infected cells are indistinguishable, and remain so through 3 weeks. Large quantities of proviral DNA in IFN-alpha-treated cells with little active transcription suggest true microbiological latency. The major potential source for IFN-alpha in HIV-infected patients is the macrophage. With any of 15 virus isolates, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, IFN-omega or IFN-beta 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-alpha after treatment with Poly-I:C, Newcastle disease virus or herpes simplex virus. In marked contrast, HIV-infected monocytes express no IFN-alpha activity or mRNA before or after treatment with any of these agents. The markedly diminished capacity of HIV-infected monocyte to produce IFN-alpha reflects a specific transcriptional block and may be an adaptive mechanism of virus to alter basic microbicidal functions of this cell.(ABSTRACT TRUNCATED AT 250 WORDS)
Meltzer
M S
MS
Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, D.C.
Baca
L
L
Turpin
J A
JA
Kalter
D C
DC
Dieffenbach
C
C
Friedman
R M
RM
Gendelman
H E
HE
D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D006678:HIV / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology
D016207:Cytokines; D007370:Interferon Type I