Hepatitis B Virus

1.1 Characteristics of Hepatitis B Virus Hepatitis B virus (HBV) is the prototype of the Hepadnaviridae family of viruses (genus Orthohepadnaviridae). Similar viruses are found in primates, woodchucks and ground squirrels, and some that are distantly related (genus Avihepadnaviridae) in various bird species. All members of this family of viruses are hepatotropic, noncytopathogenic and very species-specific. They cause persistent infections with hightiter viremia. Orthohepadnaviridae can cause acute and chronic hepatitis as well as hepatocellular carcinoma. HBV is a spherical particle with a diameter of between 42 and 45 nm. It consists of an icosahedral nucleocapsid (the core) and an outer shell made up of lipids and proteins. Hepatitis B surface antigen (HBsAg) is the main antigen of the viral envelope. It is made up of small (SHBs), medium (MHBs) and large (LHBs) HBs protein with the domains S, preS2 and preS1 (fig. 1). In addition to the virions, the blood of infected individuals also contains spherical and filamentous HBs particles with a diameter of 22 nm and without nucleocapsid. These occur in numbers approximately 1,000 times greater than the number of virions. The nucleocapsid is formed by HBcAg. In addition to viral DNA, this ‘core particle’ contains an HBV-specific DNA polymerase and a host-coded protein kinase. A soluble form of HBcAg released into the plasma is known as the HBe antigen (HBeAg). HBV occurs in at least 7 genotypes (A–G) the distribution of which varies according to geographic region. The S domain of HBsAg also has the subtype d or y and w1–4 or r determinants. In patients with high-titer viremia, the variability of HBV is not particularly great, but increases under immunoselection. The virus genome is a circular, partially double-stranded DNA molecule made up of around 3,200 bases. At the 5' end of the coding strand (minus strand), it contains covalently bound viral DNA polymerase as a protein primer for DNA synthesis, with an RNA primer at the 5' end of the plus strand. The minus strand is synthesized by reverse transcription of the pregenomic HBV RNA. HBV can be inactivated by lipid-dissolving organic solvents or by temperatures exceeding 60 °C. Because the proteins in the viral envelope are covalently bonded and contain relatively little lipid, HBV is more stable than other enveloped viruses [1, 2].