Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0035924
Title: The HIV matrix protein p17 subverts nuclear receptors expression and induces a STAT1-dependent proinflammatory phenotype in monocytes
Authors: Renga B.
Francisci D.
D'Amore C.
Schiaroli E.
Mencarelli A. 
Cipriani S.
Baldelli F.
Fiorucci S.
Keywords: CD36 antigen
CD40 antigen
CD86 antigen
cell nucleus receptor
farnesoid X receptor
intercellular adhesion molecule 1
Janus kinase 1
monocyte chemotactic protein 1
peptide vaccine
peroxisome proliferator activated receptor gamma
protein p17
receptor for activated C kinase 1
recombinant protein
STAT1 protein
2,4 thiazolidinedione derivative
3 [2 [2 chloro 4 [3 (2,6 dichlorophenyl) 5 isopropyl 4 isoxazolylmethoxy]phenyl]vinyl]benzoic acid
CD14 antigen
cell receptor
cell surface receptor
drug derivative
farnesoid X receptor
farnesoid X-activated receptor
fludarabine
Gag protein
GNB2L1 protein, human
guanine nucleotide binding protein
Human immunodeficiency virus antigen
isoxazole derivative
Janus kinase
p17 protein, Human Immunodeficiency Virus Type 1
peroxisome proliferator activated receptor gamma
rosiglitazone
STAT1 protein
STAT1 protein, human
tumor protein
vidarabine
article
controlled study
down regulation
gene control
gene expression
human
human cell
Human immunodeficiency virus 1
Human immunodeficiency virus infected patient
Human immunodeficiency virus infection
inflammation
lipid metabolism
macrophage
monocyte
promoter region
protein expression
signal transduction
vaccination
atherosclerosis
cell line
cell separation
drug effect
drug potentiation
enzymology
gene expression regulation
genetics
Human immunodeficiency virus infection
immunology
inflammation
metabolism
pathology
phenotype
phosphorylation
serodiagnosis
Human immunodeficiency virus 1
Antigens, CD14
Atherosclerosis
Cell Line
Cell Separation
gag Gene Products, Human Immunodeficiency Virus
Gene Expression Regulation
GTP-Binding Proteins
HIV Antigens
HIV Infections
HIV-1
Humans
Inflammation
Isoxazoles
Janus Kinases
Lipid Metabolism
Macrophages
Monocytes
Neoplasm Proteins
Neutralization Tests
Phenotype
Phosphorylation
PPAR gamma
Receptors, Cell Surface
Receptors, Cytoplasmic and Nuclear
Signal Transduction
STAT1 Transcription Factor
Thiazolidinediones
Vaccination
Vidarabine
Issue Date: 2012
Citation: Renga B., Francisci D., D'Amore C., Schiaroli E., Mencarelli A., Cipriani S., Baldelli F., Fiorucci S. (2012). The HIV matrix protein p17 subverts nuclear receptors expression and induces a STAT1-dependent proinflammatory phenotype in monocytes. PLoS ONE 7 (4) : e35924. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0035924
Rights: Attribution 4.0 International
Abstract: Background: 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. Aim: 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. Results: 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 PPAR?) 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 a promoter-dependent regulation of STAT-1 target genes. These effects are abrogated by sera obtained from HIV-infected persons vaccinated with a p17 peptide. Ligands for FXR and PPAR? counteract the effects of p17. Conclusions: The results of this study show that HIV p17 highjacks a Rack-1/Jak-1/STAT-1 pathway in macrophages, and that the activation of this pathway leads to a simultaneous dysregulation of immune and metabolic functions. The binding of STAT-1 to specific responsive elements in the promoter of PPAR? and FXR and MCP-1 shifts macrophages toward a pro-atherogenetic phenotype characterized by high levels of expression of the scavenger receptor CD36. The present work identifies p17 as a novel target in HIV therapy and grounds the development of anti-p17 small molecules or vaccines. © 2012 Renga et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161986
ISSN: 19326203
DOI: 10.1371/journal.pone.0035924
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications
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