Hepatitis A virus (HAV) is a small, naked virus that reaches the liver and replicates inside liver cells without killing them directly. The liver injury, and most of the symptoms, come from the immune response that clears the infected cells, which is also why the infection is self-limiting and never becomes chronic.
The virus
HAV carries a positive-sense, single-stranded RNA genome of approximately 7470 nucleotides that acts directly as mRNA once it is inside a cell. A VPg protein is attached to the 5’ end of the RNA, and the 3’ end is polyadenylated. The genome is enclosed in a small icosahedral capsid built from the VP1 to VP4 proteins, and there is no lipid envelope, so HAV is a naked virus. This capsid is unusually stable: it survives low pH and high temperature, which lets the virus pass through the stomach and persist in contaminated water and in food-processing steps that inactivate many other viruses.
Entry and replication
HAV is acquired by the fecal-oral route and reaches the liver through the bloodstream. It attaches to HAV-cell receptor 1 (HAVCR-1), a receptor expressed on liver cells and T cells, entering through the epithelial cells of the intestine and possibly also through the epithelium of the nasopharynx. Inside the liver it replicates mainly in the hepatocytes and Kupffer cells. Replication is not directly cytolytic, meaning the infected cell is usually not destroyed by the virus itself, and new virions are released by exocytosis to infect further cells.
Immune clearance
Because the virus does not destroy the cells it infects, it is the immune system that ends the infection. NK cells and cytotoxic T cells recognise and eliminate the infected hepatocytes, and this immune attack, more than the virus itself, produces the hepatitis. With the infected cells cleared, no reservoir of virus remains, so unlike HBV and HCV, HAV cannot establish a chronic infection, and unlike HBV it is not linked to hepatic cancer.