Abstract
Recent interest in the origins and subsequent evolution of the hepatitis B virus (HBV) has strengthened with the discovery of ancient HBV sequences in fossilized remains of humans dating back to the Neolithic period around 7,000 years ago. Metagenomic analysis identified a number of African non-human primate HBV sequences in the oldest samples collected, indicating that human HBV may have at some stage, evolved in Africa following zoonotic transmissions from higher primates. Ancestral genotype A and D isolates were also discovered from the Bronze Age, not in Africa but rather Eurasia, implying a more complex evolutionary and migratory history for HBV than previously recognized. Most full-length ancient HBV sequences exhibited features of inter genotypic recombination, confirming the importance of recombination and the mutation rate of the error-prone viral replicase as drivers for successful HBV evolution. A model for the origin and evolution of HBV is proposed, which includes multiple cross-species transmissions and favors subsequent recombination events that result in a pathogen and can successfully transmit and cause persistent infection in the primate host.
Highlights
Infection of the human host with the hepatitis B virus (HBV) can result in a diverse spectrum of clinical outcomes ranging from asymptomatic hepatitis through to cirrhotic liver disease and hepatocellular carcinoma (HCC)
Subgenotype A1 is found mainly in Africa, Asia, and Latin America with dispersal outside Africa suggested to have occurred as a result of the slave trade (Kramvis and Paraskevis, 2013), while A2 is in Europe and North America (Sugauchi et al, 2004); B1 is found in Japan, especially in the south, while B2, a recombinant with genotype C in the precore-core region, is found in the rest of Asia (Sugauchi et al, 2004); C1 is the dominant strain in South and Southeast Asia, while C2 is found mainly in North Asia especially Korea (Huy et al, 2004; Chan et al, 2005)
It is interesting to note that Datta, (2020) observed components of chimpanzees and subgenotype C2 HBV in ancient HBV (aHBV) samples from the Bronze Age (RISE 386/387) that were distantly related to the ancestral genotype A, from around 4 kya isolated from Bulanovo, Russia
Summary
Recent interest in the origins and subsequent evolution of the hepatitis B virus (HBV) has strengthened with the discovery of ancient HBV sequences in fossilized remains of humans dating back to the Neolithic period around 7,000 years ago. Metagenomic analysis identified a number of African non-human primate HBV sequences in the oldest samples collected, indicating that human HBV may have at some stage, evolved in Africa following zoonotic transmissions from higher primates. Most full-length ancient HBV sequences exhibited features of inter genotypic recombination, confirming the importance of recombination and the mutation rate of the error-prone viral replicase as drivers for successful HBV evolution. A model for the origin and evolution of HBV is proposed, which includes multiple cross-species transmissions and favors subsequent recombination events that result in a pathogen and can successfully transmit and cause persistent infection in the primate host
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