Hepatitis E virus. Comparison of 'New and Old World' isolates.

The etiologic agent responsible for epidemics of enterically-transmitted non-A, non-B hepatitis has been molecularly characterized as the hepatitis E virus (HEV). The cloning of a portion of the Burma strain of HEV (HEV(B); 'Old World' strain) has been described together with the isolation of a contiguous overlapping set of cDNA clones representing the entire viral genome. Our studies have led to a model for the genomic organization of this positive strand, polyadenylated, RNA virus. Molecular clones encompassing the entire genome were also isolated from a cDNA library made from the Mexico strain of HEV (HEV(M); 'New World' strain). The translated nucleotide sequence of the Mexico isolate confirmed the genomic organization as first interpreted for HEV(B). This refers to the utilization of at least three different discontinuous open reading frames for protein expression and their apparent organization into 5' nonstructural and 3' structural gene regions. The comparison of the two strains identified a localized area of divergent nucleic and amino acid sequence that was previously reported in the region encoding the nonstructural gene(s) (ORF1). The HEV expression strategy involves at least two subgenomic poly-A transcripts that are co-terminal with the 3' end of the virus. Cross-reactive (type-common) epitopes are shared between the two divergent strains. It will be important to determine in future studies if any correlation exist between the viral pathobiology in animals or humans and the primary sequence of the virus.