Inflammatory response of endothelial cells to hepatitis C virus recombinant envelope glycoprotein 2 protein exposure

Abstract

The hepatitis C virus (HCV) encodes approximately 10 different structural and non-structural proteins, including the envelope glycoprotein 2 (E2). HCV proteins, especially the envelope proteins, bind to cell receptors and can damage tissues. Endothelial inflammation is the most important determinant of fibrosis progression and, consequently, cirrhosis. The aim of this study was to evaluate and compare the inflammatory response of endothelial cells to two recombinant forms of the HCV E2 protein produced in different expression systems (Escherichia coli and Pichia pastoris). We observed the induction of cell death and the production of nitric oxide, hydrogen peroxide, interleukin-8 and vascular endothelial growth factor A in human umbilical vein endothelial cells (HUVECs) stimulated by the two recombinant E2 proteins. The E2-induced apoptosis of HUVECs was confirmed using the molecular marker PARP. The apoptosis rescue observed when the antioxidant N-acetylcysteine was used suggests that reactive oxygen species are involved in E2-induced apoptosis. We propose that these proteins are involved in the chronic inflammation caused by HCV.

Modulation of Cell Death Pathways by Hepatitis C Virus Proteins in Huh7.5 Hepatoma Cells

“…The data on the involvement of these proteins in apoptosis is scarce. However, most authors conclude that E1/E2 pro-apoptotic actions during their expression in various cell systems takes place due to both outer TNF-dependent [ 33 ] and inner mitochondrial pathways [ 33 , 34 , 35 ]. Since we previously observed the enhanced TNF-α production in E1/E2-overexpressing Huh7.5 cells, apoptosis is likely to be mediated by an outer pathway [ 23 ].…”

Recombinant hepatitis C virus-envelope protein 2 interactions with low-density lipoprotein/CD81 receptors

“…HUVEC (ATCC ® CRL-2873™) and ECV304 cells (ATCC ® CRL-1998 TM ) were used to analyse viral binding to host receptors. All cell lines were grown according to Urbaczek et al (2014) .…”

“…The E2B protein was expressed in E. coli and the E2Y protein was expressed in P. pastoris . Cloning, expression and purification were performed according to Urbaczek et al (2014) .…”

Hepatitis C virus and cardiovascular: A review

“…Hepatic steatosis and visceral obesity could contribute to this inflammatory status by prompting production of reactive oxygen species and inflammatory cytokines [18] . Along this line, endothelial damage directly related to the HCV infection [58] , [59] , or expression of a vasculitis due to mixed cryoglobulinemia [60] could further contribute to the link between HCV infection and higher cardiovascular risk.…”