title: Intergenotypic chimeric hepatitis E viruses (HEVs) with the genotype 4 human HEV capsid gene in the backbone of genotype 3 swine HEV are infectious in pigs.
abstract: Genotypes 1 and 2 hepatitis E virus (HEV) infect only humans whereas genotypes 3 and 4 HEV infect both humans and pigs. To evaluate the mechanism of cross-species HEV infection between humans and swine, in this study we constructed five intergenotypic chimeric viruses and tested for their infectivity in vitro and in pigs. We demonstrated that chimeric viruses containing the ORF2 capsid gene either alone or in combination with its adjacent 5' junction region (JR) and 3' noncoding region (NCR) from a genotype 4 human HEV in the backbone of a genotype 3 swine HEV are replication-competent in Huh7 cells and infectious in HepG2/C3A cells and in pigs, and thus supporting the hypothesis that genotypes 3 and 4 human HEV are of swine origin. However, chimeric viruses containing the JR+ORF2+3' NCR of genotypes 3 or 4 HEV in the backbone of genotype 1 human HEV failed to infect pigs, suggesting that other genomic regions such as 5' NCR and ORF1 may also be involved in HEV cross-species infection. The results from this study provide the first experimental evidence of the exchangeability of the capsid gene between genotype 3 swine HEV and genotype 4 human HEV, and have important implications for understanding the mechanism of HEV cross-species infection.
authors.affiliation: Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, 1981 Kraft Drive, Blacksburg, VA 24061, United States.
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Feagins
authors.forename: Laura
authors.initials: L
authors.lastname: Córdoba
authors.forename: Brent J
authors.initials: BJ
authors.lastname: Sanford
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Dryman
authors.forename: Yao-Wei
authors.initials: YW
authors.lastname: Huang
authors.forename: Tanya
authors.initials: T
authors.lastname: LeRoith
authors.forename: Suzanne U
authors.initials: SU
authors.lastname: Emerson
authors.forename: Xiang-Jin
authors.initials: XJ
authors.lastname: Meng
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D023061:Gene Order; D005838:Genotype; D056945:Hep G2 Cells; D016751:Hepatitis E / Q000662:veterinary* / Q000821:virology; D016752:Hepatitis E virus / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D013552:Swine; D013553:Swine Diseases / Q000821:virology*; D014766:Viremia; D017201:Virus Shedding
chemical_list: D036022:Capsid Proteins; D007074:Immunoglobulin G