Human hepatitis A virus is united with a host of relations.

The History of HAV Earliest descriptions of epidemic liver disease, most likely due to hepatitis A virus (HAV), can be found in ancient Chinese literature, and similar observations, often in association with conflict and social disruption, have appeared on many occasions. However, evidence that the infection was of viral etiology was not obtained until human volunteer experiments were conducted during and shortly after World War II. The ability of the virus to infect subhuman primates was demonstrated in 1967 (1), and the first in vitro cell culture was reported in 1979 (2). The virus was finally visualized by electron microscopic examination of stool specimens from human volunteers in 1973 (3). The virus particles were ∼30 nm in diameter and resembled picornaviruses morphologically. Subsequent molecular characterization of the RNA genome confirmed that the virus is indeed a member of the picornaviruses; a large family of single-stranded, positive-sense RNA viruses. However, many features of HAV serve to distinguish it from typical picornaviruses, and it has long occupied a phylogenetic relationship on the periphery of the picornavirus family (4). In addition to its unique properties, HAV is unusually highly conserved; for example, there is a single serotype with minimal antigenic variation. The unique properties and apparent phylogenetic isolation have made the evolutionary relationships of HAV to other picornaviruses a puzzle. However, in PNAS, Drexler et al. (5) have dramatically changed this situation with a report of the identification of a plethora of new viruses that are clearly closely related to human HAV but were isolated from a wide range of small mammals. HAV causes self-limiting infection of the liver and is transmitted by the feco-oral route. There is no evidence of long-term persistence of infection, as is typically associated with hepatotrophic viruses that are transmitted parenterally, such as hepatitis B and C viruses. HAV is resistant to high temperature and extremes of pH, and, as a consequence, it survives well in the environment and can be highly concentrated by filter-feeding molluscs. Consumption of contaminated molluscs has been associated with extensive epidemics of hepatitis A, for example, in China, where many thousands have been hospitalized as a consequence. A chemically inactivated vaccine produced from virus grown in tissue culture has been available for many years. Despite its high cost of manufacture, the vaccine is very effective as a consequence of the lack of antigenic variation