Human hepatitis A virus is united with a host of relations

Abstract

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 …