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J Gen Virol 85 (2004), 2943-2952; DOI 10.1099/vir.0.80304-0

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© 2004 Society for General Microbiology

Characterization of the complete genomic sequence of genotype II hepatitis A virus (CF53/Berne isolate)

Ling Lu1,{dagger}, Karen Z. Ching1,{ddagger}, Vanessa Salete de Paula1,§, Tatsunori Nakano1,||, Gunter Siegl2, Manfred Weitz2,# and Betty H. Robertson1

1 Laboratory Branch, Division of Viral Hepatitis, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, MS C12, Atlanta, GA 30333, USA
2 Institut für Klinische Mikrobiologie und Immunologie, St Gallen, Switzerland

Correspondence
Betty H. Robertson
bjr1{at}cdc.gov

The complete genomic sequence of hepatitis A virus (HAV) CF53/Berne strain was determined. Pairwise comparison with other complete HAV genomic sequences demonstrated that the CF53/Berne isolate is most closely related to the single genotype VII strain, SLF88. This close relationship was confirmed by phylogenetic analyses of different genomic regions, and was most pronounced within the capsid region. These data indicated that CF53/Berne and SLF88 isolates are related more closely to each other than are subtypes IA and IB. A histogram of the genetic differences between HAV strains revealed four separate peaks. The distance values for CF53/Berne and SLF88 isolates fell within the peak that contained strains of the same subtype, showing that they should be subtypes within a single genotype. The complete genomic data indicated that genotypes II and VII should be considered a single genotype, based upon the complete VP1 sequence, and it is proposed that the CF53/Berne isolate be classified as genotype IIA and strain SLF88 as genotype IIB. The CF53/Berne isolate is cell-adapted, and therefore its sequence was compared to that of two other strains adapted to cell culture, HM-175/7 grown in MK-5 and GBM grown in FRhK-4 cells. Mutations found at nucleotides 3889, 4087 and 4222 that were associated with HAV attenuation and cell adaptation in HM175/7 and GMB strains were not present in the CF53/Berne strain. Deletions found in the 5'UTR and P3A regions of the CF53/Berne isolate that are common to cell-adapted HAV isolates were identified, however.

The GenBank/EMBL/DDBJ accession numbers for the CF53/Berne sequences reported in this manuscript are AY644671AY644673 and AY644676.

{dagger}Present address: Division of Gastroenterology/Hepatology, Kansas University Medical Center, 4035 Delp MS1023, Kansas City, KS 66160, USA.

{ddagger}Present address: Respiratory and Enterovirus Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC, 1600 Clifton Road NE, MS G-10, Atlanta, GA 30333, USA.

§Present address: Oswaldo Cruz Foundation, Department of Virology, Av. Brasil 4365, 21045-900 Rio de Janeiro, Brazil.

||Present address: Department of Internal Medicine, Ichinomiya Nishi Hospital, Okucho Origuchinishi 89-1, Ichinomiya, Aichi 491-0201, Japan.

Present address: Seeblickstrasse 17, CH 9402 Mörschwil, Switzerland.

#Present address: Swissmedic, Schweizerisches Heilmittelinstitut, Berne, Switzerland.




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