Ancient hepatitis B may hold clues to viral evolution, spread

By Liam Davenport

The evolution of the hepatitis B virus (HBV) and its possible migration have become clearer with the sequencing of the oldest sample of the virus, isolated from a mummified 16^th-century Korean child, say scientists.

Noting that there are a number of HBV genotypes and subgenotypes with specific geographic distributions, and that Korea is endemic for HBV almost exclusively for genotype C, Daniel Shouval, (Hadassah-Hebrew University Hospital, Jerusalem, Israel) and colleagues studied tissue samples from the mummy of the infected child, aged between 4.5 and 6.6 years.

The team conducted an endoscopic examination of the child and examined the ancient DNA obtained from biopsy samples of the liver for both the presence of HBV DNA and to amplify the entire viral genome. The ancient HBV DNA isolate was then compared with contemporary HBV DNA.

Sequencing the entire ancient HBV genome from 24 liver tissue samples, the researchers classified the virus as genotype C2. Nucleotide and amino acid analyses suggested that the ancient HBV DNA sequences were highly similar to published contemporary HBV genotype C2 DNA from Korea, Japan, and China, and significantly different from HBV C1 sequences from Thailand, Vietnam, and Myanmar.

The highest similarity between the ancient and contemporary sequences was seen with Korean samples, at 97%. Nevertheless, there were distinctive differences between ancient HBV and contemporary HBV C2 DNA along four open reading frames.

The calculated time of most common recent ancestor indicated that the ancient HBV sequence evolved at least 3000 years ago, possibly earlier, which supports the findings of previous studies on the timeframe of human HBV DNA in East Asia.

The team summarizes in Hepatology: "The complete sequence obtained probably represents a wild-type HBV pathogen without pre-core mutations, which infected the population during the Joseon Dynasty in Korea about 400-500 years ago. Based on our analysis, the virus most probably originated in China and/or Japan and spread to Korea.

"The observed genetic diversity of the recovered ancient HBV DNA as compared to contemporary isolates is most likely a result of a natural evolutionary process and not an iatrogenic pharmacologic pressure as observed in patients treated with modern anti-viral agents."

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