The HIV matrix protein p17 subverts nuclear receptors expression and induces a STAT1-dependent proinflammatory phenotype in monocytes.

PloS One
Barbara RengaStefano Fiorucci

Abstract

Long-term remission of HIV-1 disease can be readily achieved by combinations of highly effective antiretroviral therapy (HAART). However, a residual persistent immune activation caused by circulating non infectious particles or viral proteins is observed under HAART and might contribute to an higher risk of non-AIDS pathologies and death in HIV infected persons. A sustained immune activation supports lipid dysmetabolism and increased risk for development of accelerated atehrosclerosis and ischemic complication in virologically suppressed HIV-infected persons receiving HAART. While several HIV proteins have been identified and characterized for their ability to maintain immune activation, the role of HIV-p17, a matrix protein involved in the viral replication, is still undefined. Here, we report that exposure of macrophages to recombinant human p17 induces the expression of proinflammatory and proatherogenic genes (MCP-1, ICAM-1, CD40, CD86 and CD36) while downregulating the expression of nuclear receptors (FXR and PPARγ) that counter-regulate the proinflammatory response and modulate lipid metabolism in these cells. Exposure of macrophage cell lines to p17 activates a signaling pathway mediated by Rack-1/Jak-1/STAT-1 and causes...Continue Reading

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Citations

Mar 16, 2013·Current Opinion in HIV and AIDS·Brigitte AutranCharline Bacchus
May 11, 2013·AIDS Research and Therapy·Laura Fernández-SenderJorge Joven
Nov 6, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Donghui LiuMark Slevin
Nov 18, 2018·Gene Therapy·Lei ChenYu-Dong Cai
Sep 29, 2020·Frontiers in Cell and Developmental Biology·Sabrina Bech MathiesenCathrine Rein Carlson
Sep 7, 2019·Cytokine·Xiaowen YuYongjun Jiang

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Methods Mentioned

BETA
dissection
phase-contrast
PCR
Co-immuneprecipitation
Immunoprecipitation assay
ChIP
density gradient centrifugation
Immunoprecipitation

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