Hepatitis C virus

Hepatitis C virusHepatitis C virus (HCV), a member of the Hepacivirus C species, is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer (hepatocellular carcinoma, abbreviated HCC) and lymphomas in humans. Hepatitis C virus (HCV), a member of the Hepacivirus C species, is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer (hepatocellular carcinoma, abbreviated HCC) and lymphomas in humans. The hepatitis C virus belongs to the genus Hepacivirus, a member of the family Flaviviridae. Until recently it was considered to be the only member of this genus. However a member of this genus has been discovered in dogs: canine hepacivirus. There is also at least one virus in this genus that infects horses. Several additional viruses in the genus have been described in bats and rodents. The hepatitis C virus particle consists of a lipid membrane envelope that is 55 to 65 nm in diameter. Two viral envelope glycoproteins, E1 and E2, are embedded in the lipid envelope. They take part in viral attachment and entry into the cell. Within the envelope is an icosahedral core that is 33 to 40 nm in diameter. Inside the core is the RNA material of the virus. E1 and E2 are covalently bonded when embedded in the envelope of HCV and are stabilized by disulfide bonds. E2 is globular and seems to protrude 6 nm out from the envelope membrane according to electron microscope images. These glycoproteins play an important role in the interactions hepatitis C has with the immune system. The hypervariable region 1 (HVR1) can be found on the E2 glycoprotein. HVR1 is flexible and quite accessible to surrounding molecules. HVR1 helps E2 shield the virus from the immune system. It prevents CD81 from latching onto its respective receptor on the virus. In addition, E2 can shield E1 from the immune system. Although HVR1 is quite variable in amino acid sequence, this region has similar chemical, physical, and conformational characteristics across many E2 glycoproteins. Hepatitis C virus has a positive sense single-stranded RNA genome. The genome consists of a single open reading frame that is 9600 nucleotide bases long. This single open reading frame is translated to produce a single protein product, which is then further processed to produce smaller active proteins. This is why on publicly available databases, such as the European Bioinformatic Institute, the viral proteome only consists of 2 proteins. At the 5' and 3' ends of the RNA are the UTR, that are not translated into proteins but are important to translation and replication of the viral RNA. The 5' UTR has a ribosome binding site or internal ribosome entry site (IRES) that initiates the translation of a very long protein containing about 3,000 amino acids. The core domain of the HCV IRES contains a four-way helical junction that is integrated within a predicted pseudoknot. The conformation of this core domain constrains the open reading frame's orientation for positioning on the 40S ribosomal subunit. The large pre-protein is later cleaved by cellular and viral proteases into the 10 smaller proteins that allow viral replication within the host cell, or assemble into the mature viral particles. Structural proteins made by the hepatitis C virus include Core protein, E1 and E2; nonstructural proteins include NS2, NS3, NS4A, NS4B, NS5A, and NS5B. The proteins of this virus are arranged along the genome in the following order: N terminal-core-envelope (E1)–E2–p7-nonstructural protein 2 (NS2)–NS3–NS4A–NS4B–NS5A–NS5B–C terminal. The mature nonstructural proteins (NS2 to NS5B) generation relies on the activity of viral proteinases. The NS2/NS3 junction is cleaved by a metal dependent autocatalytic proteinase encoded within NS2 and the N-terminus of NS3. The remaining cleavages downstream from this site are catalysed by a serine proteinase also contained within the N-terminal region of NS3.