Genetic identification and characterization of a novel virus related to human hepatitis E virus from chickens with hepatitis-splenomegaly syndrome in the United States

Hepatitis-splenomegaly (HS) syndrome is an emerging disease in chickens in North America; the cause of this disease is unknown. In this study, the genetic identification and characterization of a novel virus related to human hepatitis E virus (HEV) isolated from bile samples of chickens with HS syndrome is reported. Based upon the similar genomic organization and significant sequence identity of this virus with HEV, the virus has been tentatively named avian HEV in order to distinguish it from human and swine HEV. Electron microscopy revealed that avian HEV is a nonenveloped virus particle of 30-35 nm in diameter. The sequence of the 3' half of the viral genome (similar to 4 kb) was determined. Sequence analyses revealed that this genomic region contains the complete 3' non-coding region, the complete genes from open reading frames (ORFs) 2 and 3, the complete RNA-dependent RNA polymerase (RdRp) gene and a partial helicase gene from ORF 1. The helicase gene is the most conserved gene between avian HEV and other HEV strains, displaying 58-61 % as and 57-60% nt sequence identities. The RdRp gene of avian HEV shares 47-50% as and 52-53% nt sequence identities and the putative capsid gene (ORF 2) of avian HEV shares 48-49% as and 48-51 % nt sequence identities with the corresponding regions of other known HEV strains. Phylogenetic analysis indicates that avian HEV is genetically related to, but distinct from, other known HEV strains. This discovery has important implications for HEV animal models, nomenclature and natural history.