Hepadnaviridae

Hepadnaviruses are a family of viruses which can cause liver infections in humans and animals. There are two recognized genera:

• Genus Orthohepadnavirus; type species: Hepatitis B virus
• Genus Avihepadnavirus; type species: Duck hepatitis B virus

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Hepadnaviruses have very small genomes of partially double-stranded, partially single stranded circular DNA. The genome consists of two uneven strands of DNA. One has a negative-sense orientation, and the other, shorter, strand has a positive-sense orientation. As it is a group 7 virus, replication involves an RNA intermediate. Three main open reading frames are encoded (ORFs) and the virus has four known genes which encode the core protein, the virus polymerase, surface antigens (preS1, preS2, and S) and the X protein. The X protein is thought to be non-structural; however, its function and significance are poorly understood.

Hepadnavirus Replication and Treatment

Hepadnaviruses have a peculiar mode of replication; they replicate through an RNA intermediate (which they transcribe back into cDNA using reverse transcriptase). The reverse transcriptase becomes covalently linked to a short 3- or 4-nucleotide primer.^[1] Most hepadnaviruses will only replicate in specific hosts, and this makes experiments using in vitro methods very difficult.

The virus binds to specific receptors on cells and the core particle enters the cell cytoplasm. This is then translocated to the nucleus, where the partially double stranded DNA is 'repaired' by the cell to form a complete circle of DNA. It then undergoes transcription by the host cell RNA polymerase and the transcript is translated by host cell ribosomes. New virus particles are formed, which acquire lipid from the endoplasmic reticulum of the host cell, and the genome is packaged within these particles, which then bud off from the cell.

Hepadnavirus-infected cells translate the protein known as the virus surface antigen many times until there is too much protein to coat the virions formed. These proteins then aggregate to form rod shapes, and it is this antigen, known as the Australian or hepatitis B surface antigen, which is released from the cell and which leads to a very strong immune response from the host. It is thought that most of the people who come into contact with the virus are able to clear the infection alone; however, there are some who cannot, and these patients progress to fulminant Hepatitis. This condition causes severe liver damage and, in very rare cases, may also lead to primary hepatocellular carcinoma[1]. The treatment for hepatitis B includes a course of alpha interferon; this is a very expensive treatment which lasts for around 12-15 weeks and makes the patient very sick. It seems that the interferon treatment aims at kick-starting the host immune response to clear the infection; it is not the drugs that clear the infection. There are reverse transcriptase inhibitors available as treatment; these drugs target the virus replication strategy by (as the name suggests) inhibiting reverse transcription. Hepatitis B infection can also be prevented by means of a recombinant Hepatitis B surface antigen vaccine.

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