Regulation of HIV-1 expression by cytokine networks in a CD4+ model of chronic infection

S. T. Butera, B. D. Roberts, T. M. Folks

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    Abstract

    Using the CD4+ model of chronic HIV-1 infection, OM-10.1, we investigated the influence of TNF-α regulatory networks on induced viral expression. Previously, OM-10.1 cultures were characterized to respond to exogenous TNF- α, as nearly 100% of the cells were activated to express HIV-1 within 24 h. In this study, OM-10.1 cells were pulse-treated, by applying exogenous factors for short periods of time and then washing, to determine if autocrine TNF-α could sustain HIV-1 activation in the absence of additional exogenous stimulation. After a TNF-α pulse treatment, the progressive increase of HIV- 1-expressing OM-10.1 cells was prevented by the continuous presence of anti- TNF-α mAb. The inductive activity of supernatant from TNF-α pulse-treated OM-10.1 cultures was completely removed by absorption on immobilized anti- TNF-α mAb. In addition, TNF-α pulse-treated OM-10.1 cells activated HIV-1 expression in untreated OM-10.1 cells when cultured across a permeable membrane indicating paracrine effects. Interestingly, if TNF-α pulse- treated OM-10.1 cells were further pulse-treated with anti-TNF-α mAb, a marked reduction in autocrine TNF-α was observed although the level of newly synthesized TNF-α mRNA remained unaffected. A similar degree of inhibition over autocrine TNF-α production was observed when soluble TNF receptors were used as the second pulse treatment in these experiments. Although the applicability of these results to in vivo chronically HIV-1-infected cells remains to be realized, these results do indicate that activated HIV-1 expression can be influenced by self-perpetuating mechanisms during periods of limited exogenous stimulation. Furthermore, physiologic mechanisms involving soluble cytokine receptors that counteract autocrine and paracrine activation of HIV-1 expression are shown here to play a regulatory role.

    Original languageEnglish (US)
    Pages (from-to)625-634
    Number of pages10
    JournalJournal of Immunology
    Volume150
    Issue number2
    Publication statusPublished - Jan 1 1993

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    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

    Cite this

    Butera, S. T., Roberts, B. D., & Folks, T. M. (1993). Regulation of HIV-1 expression by cytokine networks in a CD4+ model of chronic infection. Journal of Immunology, 150(2), 625-634.