Hepatitis C virus (HCV) is a member of the Flaviviridae family, genus hepacivirus. HCV has been thought to be the only member of this genus until some other members was found recently. HCV causes hepatitis C, a liver disease, and can ultimately result in liver cirrhosis, hepatic failure or hepatocellular carcinoma. More than 170 million people were injected by HCV all over the world and hundreds of thousands of them were dead for this each year. The growth of HCV in cultured cells is difficult and it is hard to find small-animal models for HCV research. These difficulties limited our knowledge of HCV.
Fig. 1 HCV particles in electric microscopy
HCV is an enveloped small virus with the particle size of 55-65nm. HCV genome consists of a positive-sense single-stranded RNA. The viral genome was covered by an icosahedral capsid. The HCV genome ORF (open reading frames) encodes at least 11 proteins, including 3 structural proteins (Core or C, E1 and E2) and eight nonstructural proteins (p7, NS2, NS3, NS4A, NS4B, NS5A, NS5B, and F). The HCV core protein is released as a precursor with 191 AA residues (23kDa, P23), and then will be cut into multiple variants (17-23kDa). It contains three domains as predicted by different theories: the N-terminal hydrophilic domain (Domain D1, 120 AA), the C-terminal hydrophobic domain (Domain D2, 50 AA) and the last peptide (about 20 AA) serves as a signal for the downstream protein E1. E1 and E2 are two type 1 transmembrane glycoproteins that are essential components of the envelope. They can assemble as non-covalent heterodimers and are necessary for viral entry and fusion.
Fig. 2 Replication of HCV (Darius Moradpour, et al. Nature Reviews Microbiology, 2007)
HCV replication occurs mainly in the hepatocytes of liver, sometimes in peripheral blood mononuclear cells. Its entry to host cells is associated by the interactions between virions and cell surface factors such as CD81, LDL receptor, DC-SIGN, SR-BI, Claudin-1, and Occludin. After the injection, HCV genome is translated into a single protein with more than 3,000 aa residues. This poly-protein chain is then proteolytically cut by viral and cellular proteases to produce all the 11 viral proteins. Two proteases, NS2 cysteine autoprotease and the NS3-4A serine protease, are encoded by HCV genome. The replication occurs on the intracellular lipid membranes. Viral RNA can be recruited into an RNA replication complex by the NS proteins to produce a negative RNA. This negative RNA then serves as a template for the production of new positive strand viral genomes. Nascent RNA can be translated, or be packed up in new HCV particles. The New virus particles are thought to bud off and released at cell surface.
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