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

Area of Science:

• Virology
• Molecular Biology
• Hepatology

Background:

• Epidemics of enterically-transmitted non-A, non-B hepatitis are caused by the hepatitis E virus (HEV).
• Molecular characterization of HEV is essential for understanding its epidemiology and developing control strategies.

Purpose of the Study:

• To molecularly characterize the hepatitis E virus (HEV).
• To determine the genomic organization and sequence of different HEV strains.
• To compare HEV strains from different geographical regions.

Main Methods:

• Cloning of cDNA representing the entire genome of HEV strains from Burma (HEV(B)) and Mexico (HEV(M)).
• Nucleotide sequencing and analysis of cloned HEV genomes.
• Bioinformatic analysis to determine genomic organization and protein expression strategies.

Main Results:

• A model for the genomic organization of HEV as a positive-strand, polyadenylated RNA virus was established.
• Both HEV(B) and HEV(M) genomes were sequenced, confirming at least three discontinuous open reading frames (ORFs) for protein expression.
• A localized area of sequence divergence was identified in the nonstructural gene region (ORF1) between the two strains.
• Cross-reactive epitopes were found to be shared between the divergent HEV strains, suggesting type-common antigenic properties.

Conclusions:

• The genomic organization of HEV involves 5' nonstructural and 3' structural gene regions, with expression via at least two subgenomic transcripts.
• Despite sequence divergence in ORF1, shared epitopes indicate potential for broad cross-protection or diagnostic utility.
• Further research is needed to correlate viral sequence variations with pathobiology in humans and animals.