title: Genetic host specificity of hepatitis E virus.
abstract: Hepatitis E virus (HEV) causes epidemic and sporadic cases of hepatitis worldwide. HEV genotypes 3 (HEV3) and 4 (HEV4) infect humans and animals, with swine being the primary reservoir. The relevance of HEV genetic diversity to host adaptation is poorly understood. We employed a Bayesian network (BN) analysis of HEV3 and HEV4 to detect epistatic connectivity among protein sites and its association with the host specificity in each genotype. The data imply coevolution among ∼70% of polymorphic sites from all HEV proteins and association of numerous coevolving sites with adaptation to swine or humans. BN models for individual proteins and domains of the nonstructural polyprotein detected the host origin of HEV strains with accuracy of 74-93% and 63-87%, respectively. These findings, taken together with lack of phylogenetic association to host, suggest that the HEV host specificity is a heritable and convergent phenotypic trait achievable through variety of genetic pathways (abundance), and explain a broad host range for HEV3 and HEV4.
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: jlara@cdc.gov.
authors.forename: James
authors.initials: J
authors.lastname: Lara
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Purdy
authors.affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Yury E
authors.initials: YE
authors.lastname: Khudyakov
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001499:Bayes Theorem; D014644:Genetic Variation; D016751:Hepatitis E / Q000635:transmission*; D016752:Hepatitis E virus / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity*; D058507:Host Specificity / Q000235:genetics*; D006801:Humans; D016366:Open Reading Frames / Q000235:genetics; D010802:Phylogeny; D016415:Sequence Alignment; D013552:Swine; D013553:Swine Diseases / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000235:genetics
chemical_list: D017361:Viral Nonstructural Proteins
keywords: Adaptation; Bayesian network; Coevolution; HEV ORFs; Hepatitis E virus; Prediction