Hepatitis B virus: pathogenesis, viral intermediates, and viral replication
Section snippets
Pathogenesis
HBV is not directly cytopathic to hepatocytes. Thus, the outcome and extent of HBV infection are largely influenced by the quality and diversity of the immune response [1], [2], [3]. The immunologic events that contribute to the control of HBV replication, clearance, or varying forms of HBV–induced liver disease including hepatocellular carcinoma (HCC) involves the activation of both the humoral and the cell-mediated arms of the immune system (Fig. 1).
In patients with self-limited acute HBV
Virion morphology
Electron microscopic examination of highly viremic serum from an HBV–infected individual typically reveals three types of virus-associated particles:
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HBV virions measuring 42 nm in diameter. The virions make up an outer envelope formed by the hepatitis B surface antigen (HBsAg). This envelope surrounds an inner nucleocapsid made up of the hepatitis B core antigen (HBcAg) that is organized to package the viral genome and associated viral polymerase;
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abundant spherical particles of around 22 nm in
Life cycle and replication of hepatitis B virus
The life cycle of hepadnaviruses is characterized by the synthesis of the 3.2-kb partially double-stranded, RC DNA genome following reverse transcription of the 3.5-kb pregenomic RNA (see Fig. 3) [46]. The detailed mechanisms of RNA–directed DNA synthesis have now been well characterized through genetic and biochemical studies and have been described in several recent reviews [24], [26], [47], [48]. In contrast, early events of the viral life cycle, including attachment, penetration, uncoating,
Summary
Although HBV has the potential to generate an almost limitless spectrum of quasispecies during chronic infection, the viability of the majority of these quasispecies is almost certainly impaired due to constraints imposed by the remarkably compact organization of the HBV genome. On the other hand, single mutations may affect more than one gene and result in complex and unpredictable effects on viral phenotype. Better understanding of the constraints imposed by gene overlap and of
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