| Hepatitis C virus (HCV) is an enveloped, positive-strand RNA virus classified within the genus Hepacivirus in the family Flaviviridae. The nonsegmented HCV genome is 9.6-kb and encodes a long polyprotein that is cleaved by cellular and viral proteases into at least 10 distinct products. The N-terminal region of this polyprotein encodes the viral structural proteins: core and two envelope glycoproteins, E1 and E2. The remainder of the polyprotein encodes nonstructural (NS) proteins: p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B. NS4A is the smallest NS protein. It encodes an N-terminal hydrophobic alpha-helix that anchors NS3-4A to cellular membranes, a middle “cofactor” peptide that forms a beta-strand and contributes to proper folding of the NS3 serine protease domain, and a C-terminal acidic region that forms an alpha-helix at low pH. |