Hepatitis C virus, alcohol and lipid droplets

Abstract

Hepatitis C virus (HCV) persistence drives the progression of HCV infection. This progression is usually asymptomatic in HCV-infected patients. For many years, clinical manifestations of HCV persistence are restricted to fatty liver followed by slow development of fibrosis, cirrhosis and hepatocellular carcinoma [1, 2]. Thus, HCV persistence is a “first hit” triggering HCV pathogenesis. There are “second hits” that stabilize the infection and cause faster progression, exacerbation of pathological features of HCV infection and poor response to anti-viral therapy. One of these “second hits” known to affect HCV pathogenesis is alcohol. Liver steatosis is common for both HCV infection and alcohol and is considered as a cofactor in development and progression of fibrosis. Hepatitis C virus is an RNA virus packaged into an enveloped virus particle. HCV polyprotein has 3000 amino acids and is co-translational and posttranslational processed by cellular and viral proteases to form three structural proteins (core, E1 and E2), an ion channel protein (p7) and six non-structural proteins (NS2, NS3, NS4A, NS4B, NS5A, NS5B) [3]. Viral RNA replication requires the formation of a membrane-associated replication complex composed on HCV non-structural proteins, RNA and cellular membranes. Enveloped HCV virions carrying a newly synthesized viral genome are formed by budding into the endoplasmic reticulum lumen and leave the cells through the secretory transGolgi pathway [4].