title: A selective defect of interferon alpha production in human immunodeficiency virus-infected monocytes.
abstract: Interferon alpha (IFN-alpha) 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-alpha during any infection is the macrophage. Thus, macrophages have the potential to produce both IFN-alpha and HIV. In this study, we examined the production of IFN-alpha and other cytokines by macrophage colony-stimulating factor (M-CSF)-treated cultured monocytes during HIV infection. Tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), IL-6, IFN-omega, or IFN-beta were not detected nor was the mRNA expressed in either uninfected or HIV-infected monocytes. However, both uninfected and HIV-infected monocytes produced high levels of each of these cytokines after treatment with synthetic double-stranded RNA [poly(I).poly(C)]. Uninfected monocytes also produced high levels of IFN-alpha after treatment with poly(I).poly(C), Newcastle disease virus, or herpes simplex virus. In marked contrast to the preceding observations, HIV-infected monocytes produced little or no IFN-alpha before or after treatment with any of these agents. The absence of detectable IFN-alpha activity and mRNA in poly(I).poly(C)-treated HIV-infected monocytes 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 double-stranded RNA or secondary to the low levels of IFN-beta and IFN-omega produced by infected cells. The markedly diminished capacity of HIV-infected monocytes to produce IFN-alpha may reflect a specific 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.
authors: Department of Cellular Immunology, Walter Reed Army Institute of Research, Rockville, Maryland 20850.
authors: H E
authors: HE
authors: Gendelman
authors: R M
authors: RM
authors: Friedman
authors: S
authors: S
authors: Joe
authors: L M
authors: LM
authors: Baca
authors: J A
authors: JA
authors: Turpin
authors: G
authors: G
authors: Dveksler
authors: M S
authors: MS
authors: Meltzer
authors: C
authors: C
authors: Dieffenbach
mesh_terms: D001483:Base Sequence; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D006678:HIV / Q000235:genetics / Q000302:isolation & purification*; D015658:HIV Infections / Q000378:metabolism*; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D009522:Newcastle disease virus / Q000502:physiology; D016133:Polymerase Chain Reaction; D012330:RNA, Double-Stranded / Q000235:genetics / Q000502:physiology
chemical_list: D016207:Cytokines; D004279:DNA, Viral; D007370:Interferon Type I; D012330:RNA, Double-Stranded; D016173:Macrophage Colony-Stimulating Factor