title: Genetic changes in hepatitis E virus of subtype 1a in patients with sporadic acute hepatitis E in Kathmandu, Nepal, from 1997 to 2002.
abstract: To investigate the genetic changes in hepatitis E virus (HEV) strains in the Kathmandu valley of Nepal, we compared the 412 nt sequence within open reading frame 2 of HEV among HEV isolates recovered from 16 patients in 1999, 14 patients in 2000 and 38 patients in 2002, and additional isolates recovered from 48 patients in 1997 whose nucleotide sequences have been previously published. All 116 HEV-viraemic samples were genotyped as 1 and subtyped further as 1a (n=85, 73 %), 1c (n=29, 25 %) and mixed infection of 1a and 1c (n=2, 2 %): subtype 1c was detected only in 1997. Among the 1a isolates, nucleotide sequence identity with the representative 1a isolate of Ne131-1997 was 96.4+/-2.4 % (mean+/-SD) in 1997, 93.9+/-1.7 % in 1999, 92.2+/-1.0 % in 2000 and 91.7+/-0.5 % in 2002, indicating gradual diversification of HEV sequences. When phylogenetic analysis of the 87 subtype 1a isolates was performed, they further segregated into five clusters, with two predominant clusters of 1a-2 and 1a-3: the annual frequency of cluster 1a-2 isolates decreased from 63 % in 1997, to 50 % in 1999, to 7 % in 2000 and no cases in 2002; cluster 1a-3 isolates were observed in all four years and its annual frequency increased from 5 % in 1997 to 95 % in 2002. Of the remaining three clusters, cluster 1a-1 was detectable only in 1997 and clusters 1a-4 and 1a-5 emerged in 2000 and 2002, respectively. These results indicate that genetic changes and take over of HEV strains may contribute to the genetic variability of HEV in the community.
authors.affiliation: Liver Foundation Nepal, Tripureswor, PO Box 3439, Kathmandu, Nepal.
authors.forename: Santosh Man
authors.initials: SM
authors.lastname: Shrestha
authors.affiliation: Liver Foundation Nepal, Tripureswor, PO Box 3439, Kathmandu, Nepal.
authors.forename: Shobhana
authors.initials: S
authors.lastname: Shrestha
authors.affiliation: Department of Medical Sciences, Toshiba General Hospital, Tokyo 140-8522, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Tsuda
authors.affiliation: Division of Virology, Department of Infection and Immunity, Jichi Medical School, Tochigi-Ken 329-0498, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nishizawa
authors.affiliation: Division of Virology, Department of Infection and Immunity, Jichi Medical School, Tochigi-Ken 329-0498, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Japanese Red Cross Saitama Blood Center, Saitama-Ken 360-0806, Japan.
authors.forename: Yuhko
authors.initials: Y
authors.lastname: Gotanda
authors.affiliation: Division of Virology, Department of Infection and Immunity, Jichi Medical School, Tochigi-Ken 329-0498, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okamoto
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D014644:Genetic Variation; D006508:Hepatitis Antibodies / Q000097:blood; D016751:Hepatitis E / Q000453:epidemiology* / Q000821:virology*; D016752:Hepatitis E virus / Q000145:classification* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D009390:Nepal / Q000453:epidemiology; D010802:Phylogeny; D015995:Prevalence; D014766:Viremia / Q000453:epidemiology / Q000821:virology
chemical_list: D006508:Hepatitis Antibodies