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1 Hepatitis Branch (A33), Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control (World Health Organization Collaborating Centre for Research and Reference in Viral Hepatitis), Atlanta, Georgia 30333
2 Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7030, U.S.A.
3 National Institute of Health, Murayama Annex, 4-7-1 Gakuen, Musashimurayama, Tokyo 208, Japan
4 Institute for Clinical Microbiology and Immunology, Frohbergstrasse 3, CH 9000 St Gallen, Switzerland
5 Department of Medical Microbiology, University of Lund, Malmo General Hospital, S-21401, Malmo, Sweden
6 Aichi Prefectural Institute of Public Health, 7-6 Nagare, Tsujimachi, Kita-Ku, Nagoya 462
7 Shizuoka Prefectural Institute of Public and Environmental Health, 4-27-2 Kita-Ando, Shizuoka 420
and8 Mie Prefectural Institute of Public Health, 3-446-34 Sakurabashi, Tsu 514, Japan
A pairwise comparison of the nucleic acid sequence of 168 bases from 152 wild-type or unique cell culture-adapted strains of hepatitis A virus (HAV) revealed that HAV strains can be differentiated genetically into seven unique genotypes (I to VII). In general, the nucleotide sequence of viruses in different genotypes differs at 15 to 25% of positions within this segment of the genome. Viruses from four of the genotypes (I, II, III and VII) were recovered from cases of hepatitis A in humans, whereas viruses from the other three genotypes (IV, V and VI) were isolated only from simian species developing a hepatitis A-like illness during captivity. Among non-epidemiologically related human HAV strains, 81 were characterized as genotype I, and 19 as genotype III. Within each of these major genotypes, there were two distinct groups (sub-genotypes), which differed in sequence at approximately 7.5% of base positions. Each genotype and sub-genotype has a characteristic amino acid sequence in this region of the polyprotein, with the most divergent genotypes differing at 10 of 56 residues. Strains recovered from some geographical regions belonged to a common (endemic) genotype, whereas strains from other regions belonged to several, probably imported, genotypes. Thus, HAV strains recovered in North America were for the most part closely related at the nucleotide sequence level, whereas in other regions, such as Japan and Western Europe, HAV strains were derived from multiple genotypes or sub-genotypes. These data indicate that patterns of endemic transmission can be differentiated from situations in which infections are imported due to travel.
Received 18 December 1991;
accepted 21 February 1992.
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