Following ingestion, HAV enters the bloodstream through the epithelium of the oropharynx or intestine. The blood carries the virus to its target, the liver, where it multiplies within hepatocytes and Kupffer cells (liver macrophages). Virions are secreted into the bile and released in stool. HAV is excreted in large quantities approximately 11 days prior to appearance of symptoms or anti-HAV IgM antibodies in the blood. The incubation period is 15–50 days and mortality is less than 0.5%. Within the liver hepatocytes the RNA genome is released from the protein coat and is translated by the cell's own ribosomes. Unlike other members of the Picornaviruses this virus requires an intact eukaryote initiating factor 4G (eIF4G) for the initiation of translation. The requirement for this factor results in an inability to shut down host protein synthesis unlike other picornaviruses. The virus must then inefficiently compete for the cellular translational machinery which may explain its poor growth in cell culture. Presumably for this reason the virus has strategically adopted a naturally highly deoptimized codon usage with respect to that of its cellular host. Precisely how this strategy works is not quite clear yet.
There is no apparent virus-mediated cytotoxicity presumably because of the virus' own requirement for an intact eIF4G and liver pathology is likely immune-mediated.
Structure
The Hepatitis virus (HAV) is a Picornavirus; it is non-enveloped and contains a single-stranded RNA packaged in a protein shell. There is only one serotype of the virus, but multiple genotypes exist. Codon use within the genome is biased and unusually distinct from its host. It also has a poor internal ribosome entry site In the region that codes for the HAV capsid there are highly conserved clusters of rare codons that restrict antigenic variability.
Transmission
The virus spreads by the fecal-oral route and infections often occur in conditions of poor sanitation and overcrowding. Hepatitis A can be transmitted by the parenteral route but very rarely by blood and blood products. Food-borne outbreaks are not uncommon, and ingestion of shellfish cultivated in polluted water is associated with a high risk of infection. Approximately 40% of all acute viral hepatitis is caused by HAV. Infected individuals are infectious prior to onset of symptoms, roughly 10 days following infection. The virus is resistant to detergent, acid (pH 1), solvents (e.g., ether, chloroform), drying, and temperatures up to 60 °C. It can survive for months in fresh and salt water. Common-source (e.g., water, restaurant) outbreaks are typical. Infection is common in children in developing countries, reaching 100% incidence, but following infection there is life-long immunity. HAV can be inactivated by: chlorine treatment (drinking water), formalin (0.35%, 37 °C, 72 hours), peracetic acid (2%, 4 hours), beta-propiolactone (0.25%, 1 hour), and UV radiation (2 μW/cm2/min).