Sunday, January 25, 2009 2:09 PM
Class VIIClass VII viruses are Double stranded DNA viruses that replicate though a single stranded RNA intermediate.
An example of a virus from class VII is hepadnaviridae.
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
Virology
Genome
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.
It has a endogeneous DNA which depends on DNA polymerase. It make use of overlapping reading frame (ORF) and has an RNA intermediate.
Replication
Hepadnaviruses 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.
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.
Pathogenesis
Hepadna virus can cause chronic or acute infection. Chronic or acute infection will on the age of infection. 90% of neonates and 50% of young children infected will have chronic infection whereas only 5% to 10% of Immuno-competent adults who were infected will develop chronic infection.
Clinical Features
Acute
Acute clinical features can be from subclinical to fulminant.
Acute symptoms:
• Loss of appetite
• Nausea
• Vomiting
• Fever
• Abdominal Pain
• Jaundice
About 90% to 95% of acutely infected adults recover without squeal and about 5% to 10% of acutely infected adults become chronically infected.
Chronic
Patients who are chronically infected will be in a chronic carrier state.
They are still potentially infectious but have not symptoms and no abnormalities on laboratory testing.
Others will have clinically apparent chronic hepatitis.
Some will go on to develop cirrosis, which is the hardening of the liver and finally, hepatocellular carcinoma.
Lab Diagnosis
Diagnosis of Hepatitis B virus infection generally made on the basis of serology.
For infected patients, there will be detectable serum hepatitis B surface antigen (HBsAg).
Hepatitis B envelop surface Antigen (HbeAg) is also detectable in acute infection which is characterised by a high rate of viral replication.
IgM antibodies against core antigen are also detectable in serum.
Subsequently, IgG antibodies against the core are produced.
As acute infection resolves, IgG antibodies against core antigen persist and IgM antibodies and HbsAg becomes undetectable.
Most people who have had acute infection that resolves continue to have IgG antibodies against core antigen for life
Acutely infected patients who do not clear Hepatitis B Virus continues to have serum HbsAg.
Diagnosis of Hepatitis B is confirmed and prognosis is assessed by liver autopsy.
Treatment
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.
Done by: Jeremy Lee