Hepatitis E virus: a non-enveloped member of the 'alpha-like' RNA virus supergroup?

Abstract At least two different forms of fecal-orally transmitted viral hepatitis have been identified and characterized at the molecular level. The first agent characterized was a picornavirus known as the hepatitis A virus (HAV). A second fecal-orally transmitted agent, the hepatitis E virus (HEV), is epidemiologically distinct, due in part to the observed and unexplained high mortality (10-20%) in pregnant women. The pathophysiologic mechanism(s) for this high mortality is unknown. The genomes of these two viruses, although both polyadenylated RNA, are representative of two very different virus families. The molecular cloning and sequencing of the full length genomes of four different geographic isolates of the hepatitis E virus has shown the virus to be a single-stranded, positive-sense RNA virus with an apparent 5′ non-structural—3′ structural genetic organization. The expression strategy of the virus involves the utilization of all three forward open reading frames as well as at least two subgenomic transcripts. The non-enveloped particle size of 27-34 nm is slightly larger than that of HAV. Certain features of the virus indicate that it is related to both the enveloped alphaviridae as well as the non-enveloped caliciviridae. The relatedness of this newly characterized genome to that of other positive-sense, single-stranded RNA viruses has revealed some very unique features, discussed here, that make the taxonomic placement of HEV problematic.