Regulation of HIV-1 Expression by Cytokine Networks in a CD4+ Model of Chronic Infection

Salvatore T. Butera, Beverly D. Roberts, Thomas M. Folks

Research output: Contribution to journalArticle

48 Citations (Scopus)

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
StatePublished - 1993
Externally publishedYes

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HIV-1
Cytokines
Infection
Cytokine Receptors
Tumor Necrosis Factor Receptors
HIV Infections
Cultured Cells
Messenger RNA
Membranes

ASJC Scopus subject areas

  • 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.

Regulation of HIV-1 Expression by Cytokine Networks in a CD4+ Model of Chronic Infection. / Butera, Salvatore T.; Roberts, Beverly D.; Folks, Thomas M.

In: Journal of Immunology, Vol. 150, No. 2, 1993, p. 625-634.

Research output: Contribution to journalArticle

Butera, ST, Roberts, BD & Folks, TM 1993, 'Regulation of HIV-1 Expression by Cytokine Networks in a CD4+ Model of Chronic Infection', Journal of Immunology, vol. 150, no. 2, pp. 625-634.
Butera, Salvatore T. ; Roberts, Beverly D. ; Folks, Thomas M. / Regulation of HIV-1 Expression by Cytokine Networks in a CD4+ Model of Chronic Infection. In: Journal of Immunology. 1993 ; Vol. 150, No. 2. pp. 625-634.
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