Distinct geographical and demographic distribution of hepatitis B virus genotypes in the Canadian Arctic as revealed through an extensive molecular epidemiological survey

Abstract

Very little is known of hepatitis B virus (HBV) in Canadian Arctic indigenous populations, where HBV was considered endemic prior to the introduction of HBV vaccine. This study expands upon an HBV seroepidemiological survey conducted between 1983 and 1985 throughout the Canadian Arctic, to characterize HBV in this population. Archived hepatitis B surface antigen (HBsAg)-positive sera (n = 401) were processed for HBV DNA, followed by sequencing and phylogenetic analysis of the HBsAg- and HBcAg-coding regions. Sixty-nine per cent of samples (277/401) were DNA positive, with most having low viral load (median 3.4 log 10 IU/mL). The predominant HBV genotype observed was genotype B (HBV/B, 75%), followed by HBV/D (24%) and HBV/A (1%). All HBV/B strains clustered within subgenotype B6, a newly recognized HBV genotype among western circumpolar Inuit and Alaska Native people. HBV/D strains included both D3 (88%) and D4 (12%) subgenotypes, while all HBV/A strains were subgenotype A2. An association of HBV genotype B with Inuit living in the eastern Arctic and an association of genotype D with First Nation (Dene) living in the western Arctic was observed. This study establishes the high prevalence of HBV/B6 and HBV/D genotypes in Arctic populations and reveals their marked distribution within the Canadian Arctic based on geographical and demographic attributes.

Serological and molecular epidemiological outcomes after two decades of universal infant hepatitis B virus (HBV) vaccination in Nunavut, Canada

“…Both HBV/B5 and HBV/D were expected in the sample population as previous studies have shown [78]. However, the HBV/A strains detected, which were most similar to subgenotype A1, have not been previously observed in Nunavut.…”

African, Amerindian and European hepatitis B virus strains circulate on the Caribbean Island of Martinique

“…More partial HBV/D4 sequences have also been described (Andernach et al, 2009, Norder et al, 2004, Osiowy et al, 2011, Santos et al, 2010 mainly in the S gene. Phylogenetic analyses with all published D4 partial sequences confirmed that Martinican strains clearly belong to the HBV/D4 subgenotype but do not form a separate cluster (data not shown).…”

Genotypes and Genetic Variability of Hepatitis B Virus

“…Subgenotype B1, found mainly in Japan [20], and B5 (previously B6) from a Canadian Inuit population [21] represent genotype B without recombination with genotype C in the precore/core region, as opposed to the remaining subgenotypes of B that have this recombination [20]. Subgenotype B1 was probably the ancestor of B5, possibly carried by indigenous peoples during migration from Siberia and Alaska to North America and Greenland [22,23]. …”

“…It is possible that D4 originated in Africa but has subsequently been replaced by other subgenotypes of D and the recombinant is a remnant of the original strain/s [30]. Subgenotype D4 carriers were significantly older than both D3 and B6 carriers [23]. Although it has been suggested that subgenotype D5 is the most ancient of the subgenotypes of D [31], this conclusion is neither supported by the relatively low intragroup divergence of this subgenotype [28], nor by the dated HBV phylogeny of the subgenotypes of D [8].…”

“…Subgenotypes D3 and ‘D6' were reclassified as a single subgenotype D3, and ‘D8' was shown to be a genotype D/E recombinant rather than a subgenotype [28]. Subgenotype D4, which is found in aboriginal populations in Papua New Guinea and Australia [12] and in a small percentage of the Canadian Inuit population [29], may be an early subgenotype dating from the time of early human intercontinental migrations. Moreover, a recombinant of subgenotype D4 has been identified in Sudan [30].…”