RNA recombination in Hepatitis delta virus: Identification of a novel naturally occurring recombinant

Background/Purpose Hepatitis delta virus (HDV) is the only animal RNA virus that has an unbranched rod-like genome with ribozyme activity. It replicates in the nucleus by host RNA polymerase via a rolling circle mechanism. Similar to many RNA viruses encoding their own RNA-dependent RNA polymerases, homologous recombination of HDV occurs in mixed-genotype infections and in cultured cells cotransfected with two HDV sequences, as demonstrated by molecular analyses. Methods Among 237 published complete genomic sequences, 34 sequences were reported from the small and isolated Miyako Island, Japan, and belonged to the Asia-specific genotypes, HDV-2 and HDV-4 (the majority of them belonged to the known Miyako Island-specific subgroup, HDV-4M). We investigated the presence of naturally occurring HDV recombinant in Miyako Island using phylogenetic and recombination analyses. Results We identified a two-switch HDV-4/4M intersubtype recombinant with an unbranched rod-like RNA genome. Conclusion Our data suggest that RNA recombination plays an important role in the rapid evolution of HDV, allowing the production of new HDV strains with correct genomic structures.