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.
Highlights
The hepatitis C virus (HCV), a member of the genus Hepacivirus in the family Flaviviridae, is a small enveloped virus that possesses a positive-sense singlestranded RNA genome of approximately 9.6 kb (Hoofnagle 2002, Penin et al 2004, Kaukinen et al 2013)
The cellular events provoked by the envelope glycoprotein 2 (E2) proteins were evaluated using annexin V and propidium iodide (PI) assays, which indicated that early apoptosis was the main cause of cell death (Fig. 3)
There is evidence that endothelial cells are directly susceptible to infection by HCV (Fletcher et al 2012) and that the damage caused by the infection leads to late complications, such as fibrosis, cirrhosis and hepatocellular carcinoma
Summary
The hepatitis C virus (HCV), a member of the genus Hepacivirus in the family Flaviviridae, is a small enveloped virus that possesses a positive-sense singlestranded RNA genome of approximately 9.6 kb (Hoofnagle 2002, Penin et al 2004, Kaukinen et al 2013). The genome has a single open reading frame (ORF) (Taylor et al 2000) encoding a polyprotein precursor of approximately 3,000 amino acid residues that is cleaved by host and viral proteases to generate approximately 10 distinct structural and non-structural proteins (Encke et al 1998, Penin et al 2004). One of these proteins is envelope glycoprotein 2 (E2), which undergoes post-translational modification after synthesis and possesses nine-11 potential glycosylation sites (Liu et al 2001, Whidby et al 2009). The aim of this study was to evaluate and compare the inflammatory response of endothelial cells [human umbilical vein endothelial cells (HUVECs)] to two recombinant forms of the HCV E2 protein produced in different expression systems
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