Complete genome sequence of a divergent strain of Tibetan frog hepatitis B virus associated to concave-eared torrent frog Odorrana tormota

Abstract

The family Hepadnaviridae is characterized by partially dsDNA circular viruses of approximately 3.2 kb, which are reverse transcribed from RNA intermediates. Hepadnaviruses (HBVs) have a broad host range which includes humans (Hepatitis B virus), other mammals (genus Orthohepadnavirus), and birds (Avihepadnavirus). HBVs host specificity has been expanded by reports of new viruses infecting fish, amphibians, and reptiles. The tibetan frog hepatitis B virus (TFHBV) was recently discovered in Nanorana parkeri (Family Dicroglossidae) from Tibet. To increase understanding of hepadnavirus in amphibian host, we identified the full-length genome of a divergent strain TFHBV-Ot associated to the concave-eared torrent frog Odorrana tormota (Family Ranidae) from China by searching deep sequencing data. TFHBV-Ot shared the genomic organization and a 76.6% overall genome nucleotide identity to the prototype TFHBV associated to N. parkeri (TFHBV-Np). TFHBV-Ot amino acid pairwise identity with TFHBV-Np predicted gene products ranged between 63.9% and 77.9%. Multiple tissue/organ specific RNAseq datasets suggest a broad tropism of TFHBV including muscles, gonads and brains. In addition, we provide for the first time evidence of virus derived small RNA from an amphibian hepadnavirus, tentatively enriched in 19-20 nt species and cytidine as first base. The results presented here expand the genetic diversity and the host range of TFHBV to Ranidae frogs, and warrant investigation on hepadnaviral infection of amphibian brains.