Hepatitis C Virus Glycoprotein-dependent Entry
H.E. Drummer and J.A. McKeating
from: Hepatitis C: Antiviral Drug Discovery and Development (Edited by: Seng-Lai Tan and Yupeng He). Caister Academic Press, U.K. (2011)
Glycoprotein E1 and E2 are type 1 transmembrane proteins that are cleaved from the polyprotein through the action of signal peptidases in the endoplasmic reticulum (ER) where they form disulfide linked and non disulfide linked heterodimers. The native folding of E1 and E2 is highly dependent on their coexpression, although a subdomain of E2 can be expressed in isolation that retains receptor binding properties (sE2). The HCV glycoproteins are distantly related to the phylogenetically related flavivirus glycoproteins prM and E, although sequence comparisons together with functional and structural studies suggest significant divergence. HCV research was severely restricted by the inability to propagate the virus in cultured cells. The recent development of the JFH-1 HCVcc system has enabled rapid discoveries in all areas of HCV research, including the discovery of viral entry factors. The detailed mechanism(s) of HCV entry into polarized cells awaits further investigation. It will be interesting to see the role of entry inhibitors in future combination therapies for the treatment of chronic HCV infection read more ...