Hepatitis B Virus Infection And Immunity

Howard C Thomas and Jennifer A Waters, Department of Medicine, Imperial College of Medicine, St Mary's Hospital, London, UK

Hepatitis B virus (HBV) infection is a major public health problem, infecting approximately 300 million people worldwide, and is a major cause of chronic liver disease and hepatocellular carcinoma (HCC). The majority of adults infected have a transient hepatitis from which they completely recover and clear the virus. Rarely the disease becomes fulminant and the patient may die. Between 5 and 10% of adults become persistently infected and develop chronic liver disease. In the majority of cases of vertical transmission the virus is not eliminated and the child becomes chronically infected, greatly increasing its risk of developing cirrhosis and HCC.

Virology

HBV is a member of the Hepadnaviridae, a related group of hepatotropic, enveloped, double-stranded DNA viruses which have small genomes. The HBV genome is 3.2 kb in size and contains four open reading frames (Figure 1). These encode the envelope (hepatitis B surface antigen, HBsAg), nucleocapsid

(hepatitis B core and 'e' antigens, HBcAg and HBeAg), DNA polymerase and X protein.

The envelope of the virus contains the large, middle and major surface proteins, which all contain the same carboxyl terminus of 226 amino acids. The middle protein has an additional 55 amino acids designated the pre-S2 region, and the large protein has a further 120 amino acids designated the pre-Sl region. All of these proteins also occur in a glycosylated form.

The core gene encodes two overlapping polypeptides. The longer of these polypeptides contains a signal peptide which directs it to the endoplasmic reticulum where the amino- and carboxy-terminal ends are cleaved and HBeAg is secreted into the circulation. The smaller polypeptide has a nucleophilic sequence at its carboxy-terminal end and associates with the RNA pregenome of the virus during the initial stage of the formation of nucleocapsids. The X open reading frame encodes a protein which has the ability to modify the transcription of both viral and host cell genes.

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