Virion Structure and Unique Genome
The hepatitis B virus is spherical. Externally, it is covered by a lipoprotein envelope, which encloses an icosahedral core (nucleocapsid) composed of 180 protein subunits.
The HBV genome has an unusual structure. It is a double-stranded circular DNA with asymmetric strands:
- Minus strand — complete, carries genetic information (contains 4 genes: P, C, S, X) and is covalently linked to the DNA polymerase enzyme.
- Plus strand — shortened to about 1/3 to 3/4 of the full length.
Upon entering the host cell, viral DNA polymerase extends the plus strand, converting the genome into a fully double-stranded structure.
Antigenic Profile
Viral antigens play a crucial role in diagnosis and understanding the stage of the disease:
- HBsAg (Surface antigen). Located in the virion envelope, composed of glycoproteins (preS1, preS2, S). Historically known as the “Australian antigen.” It can circulate in the blood both as part of intact virions and as empty subviral particles. It stimulates the production of protective virus-neutralizing antibodies (anti-HBs).
- HBcAg (Core antigen). The internal protein of the nucleocapsid. In free form, it is not detectable in the blood; it can only be identified in liver biopsy samples.
- HBeAg. A secreted derivative of the HBc antigen. Its appearance in the blood is a precise marker of active viral replication and high patient infectivity.
- HBxAg. A transactivator protein. Its accumulation is linked to the risk of developing hepatocellular carcinoma (liver cancer) because it binds and inactivates the tumor suppressor protein p53.
Life Cycle and Forms of Infection
The incubation period lasts from 3 to 6 months. The virus enters hepatocytes via endocytosis, using serum albumin as a bridge between cell receptors and the preS2 antigen.
Subsequent development can follow two pathways:
- Integrative infection (carrier state). Viral DNA integrates into the host cell chromosome (provirus). Only HBsAg is synthesized. This specific form increases the risk of malignant transformation (cancer).
- Productive infection. Active assembly of new virions takes place. A unique feature of this process: pregenomic RNA is synthesized using the minus-DNA strand as a template, and then viral DNA polymerase generates a new minus-DNA strand via reverse transcription. This is accompanied by the release of HBeAg into the bloodstream.
Immunopathogenesis and Outcomes
The hepatitis B virus itself lacks cytopathic effects — it does not directly destroy infected hepatocytes. Liver damage is exclusively immune-mediated.
Viral peptides combined with MHC class I molecules are displayed on the surface of infected cells. Cytotoxic CD8+ T lymphocytes recognize this "tag" and destroy the cell. Massive hepatocyte lysis leads to inflammation and jaundice.
Infection outcomes:
- Recovery with lifelong immunity (virus elimination is driven by anti-HBs and the cellular immune response).
- Progression to chronic infection (in 5–10% of adults and 50–90% of infants infected during their first year of life).
- Fulminant hepatitis (approx. 1% of cases, associated with high mortality).
Epidemiology and Prevention
The infection is distributed worldwide. The reservoir consists of over 400 million carriers and infected individuals.
Routes of transmission:
- Parenteral (medical procedures, blood transfusions, tattoos).
- Natural (sexual, household contact via razors and toothbrushes, vertical transmission from mother to child).
Specific prophylaxis involves a recombinant genetic-engineering vaccine containing purified HBsAg. Newborns are vaccinated within the first 24 hours of life. Immunity persists for at least 7 years.