E1

The envelope glycoprotein E1 protein is a highly glycosylated transmembrane protein that tightly associates with the E2 glycoprotein to form the envelope glycoprotein E1-E2 heterodimer. The E1 protein plays a role in multiple steps in the HCV replication cycle, including attachment to the host cell, endosome-lipid membrane fusion, and assembly. The role for E1 in attachment may involve binding to host apoproteins or possibly CD36. In addition, E1 assists E2 as it binds with host receptors by maintaining an E1-E2 structural conformation favorable for receptor binding. Following endocytosis of the HCV particle, the acidic environment in the endosome stimulates conformational changes in E1 and E2, which generates fusion of the endosomal membrane with the viral envelope and release of the HCV RNA into the cytoplasm. Recent studies also suggest the E1 protein interacts with several other viral proteins to coordinate the HCV assembly process.