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 language | English (US) |
|---|---|
| Pages (from-to) | 625-634 |
| Number of pages | 10 |
| Journal | Journal of Immunology |
| Volume | 150 |
| Issue number | 2 |
| State | Published - 1993 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
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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 journal › Article
}
TY - JOUR
T1 - Regulation of HIV-1 Expression by Cytokine Networks in a CD4+ Model of Chronic Infection
AU - Butera, Salvatore T.
AU - Roberts, Beverly D.
AU - Folks, Thomas M.
PY - 1993
Y1 - 1993
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0027229209&partnerID=8YFLogxK
M3 - Article
C2 - 8380428
AN - SCOPUS:0027229209
VL - 150
SP - 625
EP - 634
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -