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GENOMIC CHARACTERISTICS AND VIRAL EVOLUTION OF HEPATITIS B VIRUS GENOTYPE B AMONG INDIGENOUS POPULATIONS LIVING IN THE ARCTIC

C Osiowy¹, Y Tanaka², M Mizokami², J Simonetti³, BJ McMahon³, GY Minuk⁴
¹National Microbiology Laboratory, Winnipeg, Manitoba; ²Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; ³Alaska Native Medical Center, Anchorage, Alaska, USA; ⁴University of Manitoba, Winnipeg, Manitoba

AIM: Hepatitis B virus (HBV) has been grouped into 8 different genotypes, A to H, each having a distinct geographic distribution. Evidence pointing toward the influence of HBV genotypes and subgenotypes on clinical outcome has been steadily accumulating. To date, two distinct subgenotypes of HBV genotype B have been reported; Bj, indigenous in Japan, and Ba, predominant in Asian regions outside Japan. Ba is distinguished by a genotype C recombination within the precore/core regions of the genome. The aim of the present study was to investigate the genomic characteristics and evolution of HBV genotype B among indigenous populations living in the Arctic.
METHODS: Sera obtained from 31 Alaskan Native Peoples and 8 Canadian Inuit adult HBV carriers were extracted for HBV DNA followed by sequence and molecular evolutionary analysis.
RESULTS: Subjects were anti-HBe positive (34/39), inactive carriers with the majority having low HBV serum levels (< 5 log copies/ml). Liver biochemistry tests were normal for all Canadian Inuit and approx. half of all Alaskan Native subjects. Phylogenetic analysis based on complete HBV sequences from 6 Alaskan Native Peoples and 8 Canadian Inuit (including two time point samples, 25 years apart), showed significant phylogenetic clustering with Japanese Bj isolates. All Arctic HBV samples had no recombination with HBV genotype C, thus confirming the distinct nature of subgenotype Bj. The precore stop codon mutation at nt 1896 was highly prevalent within the subject group (78% Alaskans, 100% Canadians), whereas the basal core promoter mutation was observed less frequently. Linear regression analysis using time point samples from Canadian Inuit estimated a mutation rate of approx. 8 x 10⁵ substitutions/site/year, indicating that these HBV/B strains diverged several hundred years previous.
CONCLUSIONS: Characteristics of genotype B HBV observed among indigenous populations living in the Arctic were highly similar to those of the HBV Bj genotype observed exclusively within Japan.

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