Hepatitis C virus (HCV) has been considered to be a significant risk factor in developing liver associated diseases including hepatocellular carcinoma all over the world. HCV is an enveloped positive strand virus comprising a complex between genomic RNA and viral envelope glycoproteins (E1 and E2), which are anchored within host derived double-layered lipid membrane surrounding the nucleocapsid composed of several copies of core protein. HCV cell entry is the first step in infection and viral replication into host cells mainly hepatocytes. HCV cell entry is a complex process involving both the viral (envelope glycoproteins E1/E2) and host factors (cellular receptors and associated factors i.e. CD81, SR-BI, LDL-R, CLDN1, Occludin, DC-SIGN, L-SIGN and Glycosaminoglycans). Besides these the expression of certain other conditions such as polarization and EWI-2 expression inhibits the viral cell entry. Exploring the mechanism of HCV entry will help to better understand the viral life cycle and possible therapeutic targets against HCV infection including viral and host factors involved in this process. New strategies such as RNAi represents a new option for targeting the host or viral factors for prevention and therapeutic against HCV infection. In the current review we try to summarize the current knowledge about mechanism and interaction of cellular and viral factors involved in HCV cell entry and its implication as therapeutic target to inhibit HCV infection.
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