title: Hepatitis E virus (HEV): strain variation in the nonstructural gene region encoding consensus motifs for an RNA-dependent RNA polymerase and an ATP/GTP binding site.
abstract: Hepatitis is transmitted by a number of infectious agents. The epidemiological characterization of waterborne or enterically transmitted non-A, non-B hepatitis (ET-NANBH) is unique when compared with other known hepatitides. We have reported on the molecular cloning of a cDNA clone derived from the etiologic agent associated with ET-NANBH, the hepatitis E virus (HEV). The complete sequence of these first molecular clones, isolated from an HEV-infected human after passage in Macaca fascicularis (cynomolgus macaques), illustrates a distant relationship to other known positive-strand RNA viruses of plants and animals. The translated major open reading frame (ORF-1) from these clones indicates that this portion of the genome encodes a polyprotein with consensus sequences found in RNA-dependent RNA polymerase and ATP/GTP binding domains. The latter activity has been associated with putative helicases of positive-strand RNA viruses. These viral-encoded enzymatic activities identify this region and ORF-1 as containing at least two different nonstructural genes involved in HEV replication. Molecular clones obtained from two other geographically distinct HEV isolates demonstrated sequence heterogeneity in this nonstructural gene region. Further study will be required to elucidate the pathogenic significance (if any) of this observed divergence in the nonstructural region.
authors.affiliation: Molecular Virology Department, Genelabs Incorporated, Redwood City, CA 94063.
authors.forename: K E
authors.initials: KE
authors.lastname: Fry
authors.forename: A W
authors.initials: AW
authors.lastname: Tam
authors.forename: M M
authors.initials: MM
authors.lastname: Smith
authors.forename: J P
authors.initials: JP
authors.lastname: Kim
authors.forename: K C
authors.initials: KC
authors.lastname: Luk
authors.forename: L M
authors.initials: LM
authors.lastname: Young
authors.forename: M
authors.initials: M
authors.lastname: Piatak
authors.forename: R A
authors.initials: RA
authors.lastname: Feldman
authors.forename: K Y
authors.initials: KY
authors.lastname: Yun
authors.forename: M A
authors.initials: MA
authors.lastname: Purdy
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D004247:DNA / Q000096:biosynthesis; D012321:DNA-Directed RNA Polymerases / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D005814:Genes, Viral; D005822:Genetic Vectors; D006160:Guanosine Triphosphate / Q000378:metabolism*; D016751:Hepatitis E / Q000382:microbiology; D016752:Hepatitis E virus / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D008252:Macaca fascicularis; D008969:Molecular Sequence Data; D012367:RNA, Viral; D012689:Sequence Homology, Nucleic Acid; D012984:Software
chemical_list: D012367:RNA, Viral; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D004247:DNA; D012321:DNA-Directed RNA Polymerases