Tu2052 Acute Liver Torsion: A Rare Case of Abdominal Pain and Elevated Liver Transaminases

Abstract

Background. Matrix proteins are essential in the HIV replication cycle. The HIV matrix protein p17 serves several functions in the viral replication cycle including the viral nuclear import at early stage of infection. In the late stage, p17 mediates the recruitment of the viral surface/transmembrane gp120/gp41 envelope protein complex into virions and targets Pr55Gag proteins to their assembly sites at the plasma membrane of infected cells. Members of the nuclear receptor superfamily exert their regulatory activity integrating regulatory effects exerted by nutrients with intermediate metabolism by positively and negatively regulating the expression of effector genes. We have previously demonstrated that HIV infection is associated with an altered expression of nuclear receptor transcriptome in human monocytes as well as that stimulation of these cells with p17 down-regulates the expression of FXR and PPARγ. Aims. To analyze the effect exerted by the HIV matrix protein p17 on nuclear receptor gene expression in HepG2 cells. Methods. Serum starved HepG2 cells were stimulated 18 hours with 2 μg/ml recombinant p17 protein. At the end of the stimulation total RNA was extracted, reverse-transcribed in cDNA and amplified using specific primers for 10 nuclear receptors. Relative mRNA expression of Fatty Acid Elongase (FAE) was also investigated. Results. HepG2 cells treated with the HIV matrix protein p17 expressed an altered pattern of nuclear receptors characterized by a profound down-regulation in the expression of PPARα, -β, -γ, RARα, RXR, LXRβ, FXR, SHP, PXR and GR. Of interest, the deregulated expression of these transcription factors was linked to reduced expression of the enzyme FAE which is involved in the elongation of fatty acids during their biosynthesis process (Figure). Conclusions. Altered expression of nuclear receptors mediating reciprocal regulation of lipid metabolism and immune function occurs in HepG2 cells under p17 administration. These data highlight a detrimental effects of HIV proteins in resetting lipid metabolism in liver cells. These data might explain detrimental effects of HIV-HCV coinfection on lipid metabolism.