Abstract
BackgroundIndigenous populations of the circumpolar Arctic are considered to be endemically infected (>2% prevalence) with hepatitis B virus (HBV), with subgenotype B5 (formerly B6) unique to these populations. The distinctive properties of HBV/B5, including high nucleotide diversity yet no significant liver disease, suggest virus adaptation through long-term host-pathogen association.MethodsTo investigate the origin and evolutionary spread of HBV/B5 into the circumpolar Arctic, fifty-seven partial and full genome sequences from Alaska, Canada and Greenland, having known location and sampling dates spanning 40 years, were phylogeographically investigated by Bayesian analysis (BEAST 2) using a reversible-jump-based substitution model and a clock rate estimated at 4.1 × 10−5 substitutions/site/year.ResultsFollowing an initial divergence from an Asian viral ancestor approximately 1954 years before present (YBP; 95% highest probability density interval [1188, 2901]), HBV/B5 coalescence occurred almost 1000 years later. Surprisingly, the HBV/B5 ancestor appears to locate first to Greenland in a rapid coastal route progression based on the landscape aware geographic model, with subsequent B5 evolution and spread westward. Bayesian skyline plot analysis demonstrated an HBV/B5 population expansion occurring approximately 400 YBP, coinciding with the disruption of the Neo-Eskimo Thule culture into more heterogeneous and regionally distinct Inuit populations throughout the North American Arctic.DiscussionHBV/B5 origin and spread appears to occur coincident with the movement of Neo-Eskimo (Inuit) populations within the past 1000 years, further supporting the hypothesis of HBV/host co-expansion, and illustrating the concept of host-pathogen adaptation and balance.
Highlights
Endemic infection (>2%) with hepatitis B virus (HBV) has been historically observed throughout Inuit and Alaska Native populations of the western circumpolar Arctic (McMahon, 2004; Minuk & Uhanova, 2003; Tulisov et al, 2007), ongoing vaccination programs, starting in the mid-1980’s to mid-1990’s, have or are expected to reduce prevalence to non-endemic levels (Huynh et al, 2014; McMahon et al, 2011)
Studies have shown several HBV genotypes circulating within Inuit or Alaska Native people of the circumpolar Arctic; subgenotype B5 (HBV/B5; formerly B6 (Kramvis, 2014)) is unique to this population and has not been found elsewhere (Osiowy, Simons & Rempel, 2013)
This clinical association, together with the distinct nucleotide diversity and mutation rate observed with HBV/B5 compared to other HBV genotypes infecting Inuit and Alaska Native populations (Kowalec et al, 2013), suggests potential pathogen attenuation within the population due to host-pathogen co-evolution (Paraskevis et al, 2013; Tedder et al, 2013)
Summary
Endemic infection (>2%) with hepatitis B virus (HBV) has been historically observed throughout Inuit and Alaska Native populations of the western circumpolar Arctic (McMahon, 2004; Minuk & Uhanova, 2003; Tulisov et al, 2007), ongoing vaccination programs, starting in the mid-1980’s to mid-1990’s, have or are expected to reduce prevalence to non-endemic levels (Huynh et al, 2014; McMahon et al, 2011). While chronic HBV infection often results in liver cirrhosis or hepatocellular carcinoma, HBV/B5 chronic infection is infrequently associated with serious adverse effects (Krarup et al, 2008; Minuk et al, 2013; Sakamoto et al, 2007) and rather, results in a ‘benign’ outcome This clinical association, together with the distinct nucleotide diversity and mutation rate observed with HBV/B5 compared to other HBV genotypes infecting Inuit and Alaska Native populations (Kowalec et al, 2013), suggests potential pathogen attenuation within the population due to host-pathogen co-evolution (Paraskevis et al, 2013; Tedder et al, 2013). In order to investigate the origin, evolution and spread of HBV/B5, spatial and temporal phylogenetic analysis of HBV sequences obtained throughout the circumpolar Arctic was performed. HBV/B5 origin and spread appears to occur coincident with the movement of Neo-Eskimo (Inuit) populations within the past 1000 years, further supporting the hypothesis of HBV/host co-expansion, and illustrating the concept of host-pathogen adaptation and balance
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