The Journal of Immunology, Vol 150, Issue 2 625-634, Copyright © 1993 by American Association of Immunologists

ARTICLES

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

ST Butera, BD Roberts and TM Folks
Retrovirus Diseases Branch, Centers for Disease Control, Atlanta, GA 30333.

Using the CD4+ model of chronic HIV-1 infection, OM-10.1, we investigated the influence of TNF-alpha regulatory networks on induced viral expression. Previously, OM-10.1 cultures were characterized to respond to exogenous TNF-alpha, 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-alpha could sustain HIV-1 activation in the absence of additional exogenous stimulation. After a TNF-alpha pulse treatment, the progressive increase of HIV-1-expressing OM-10.1 cells was prevented by the continuous presence of anti-TNF-alpha mAb. The inductive activity of supernatant from TNF-alpha pulse-treated OM-10.1 cultures was completely removed by absorption on immobilized anti-TNF-alpha mAb. In addition, TNF-alpha 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-alpha pulse-treated OM-10.1 cells were further pulse-treated with anti-TNF- alpha mAb, a marked reduction in autocrine TNF-alpha was observed although the level of newly synthesized TNF-alpha mRNA remained unaffected. A similar degree of inhibition over autocrine TNF-alpha 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.

This article has been cited by other articles:

				E. Cassol, M. Alfano, P. Biswas, and G. Poli Monocyte-derived macrophages and myeloid cell lines as targets of HIV-1 replication and persistence J. Leukoc. Biol., November 1, 2006; 80(5): 1018 - 1030. [Abstract] [Full Text] [PDF]

				P. C. Guenthner, W. E. Secor, and C. S. Dezzutti Trichomonas vaginalis-Induced Epithelial Monolayer Disruption and Human Immunodeficiency Virus Type 1 (HIV-1) Replication: Implications for the Sexual Transmission of HIV-1 Infect. Immun., July 1, 2005; 73(7): 4155 - 4160. [Abstract] [Full Text] [PDF]

				K. Devadas, N. J. Hardegen, L. M. Wahl, I. K. Hewlett, K. A. Clouse, K. M. Yamada, and S. Dhawan Mechanisms for Macrophage-Mediated HIV-1 Induction J. Immunol., December 1, 2004; 173(11): 6735 - 6744. [Abstract] [Full Text] [PDF]

				S. D. Lawn, S. T. Butera, and T. M. Folks Contribution of Immune Activation to the Pathogenesis and Transmission of Human Immunodeficiency Virus Type 1 Infection Clin. Microbiol. Rev., October 1, 2001; 14(4): 753 - 777. [Abstract] [Full Text] [PDF]

				K. Hestdal, P. Aukrust, F. Muller, E. Lien, V. Bjerkeli, T. Espevik, and S. S. Froland Dysregulation of Membrane-Bound Tumor Necrosis Factor-alpha and Tumor Necrosis Factor Receptors on Mononuclear Cells in Human Immunodeficiency Virus Type 1 Infection: Low Percentage of p75-Tumor Necrosis Factor Receptor Positive Cells in Patients With Advanced Disease and High Viral Load Blood, October 1, 1997; 90(7): 2670 - 2679. [Abstract] [Full Text] [PDF]