PT  - JOURNAL ARTICLE
AU  - Wei-Shan Chang
AU  - John H.-O. Pettersson
AU  - Callum Le Lay
AU  - Mang Shi
AU  - Nathan Lo
AU  - Michelle Wille
AU  - John-Sebastian Eden
AU  - Edward Holmes
TI  - Novel hepatitis D-like agents in vertebrates and invertebrates
AID  - 10.1101/539924
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 539924
4099  - http://biorxiv.org/content/early/2019/02/04/539924.short
4100  - http://biorxiv.org/content/early/2019/02/04/539924.full
AB  - Hepatitis delta virus (HDV) is the smallest known RNA virus and encodes a single protein. Until recently, HDV had only been identified in humans, where it is strongly associated with co-infection with hepatitis B virus (HBV). However, the recent discovery of HDV-like viruses in metagenomic samples from birds and snakes suggests that this virus has a far longer evolutionary history. Herein, using additional meta-transcriptomic data, we show that highly divergent HDV-like viruses are also present in fish, amphibians and invertebrates. Notably, the novel viruses identified here share HDV-like genomic features such as a small genome size of ~1.7kb in length, circular genomes, and self-complementary, unbranched rod-like structures. Coiled-coil domains, leucine zippers, conserved residues with essential biological functions and isoelectronic points similar to those in the human hepatitis delta virus antigens (HDAgs) were also identified in the putative non-human HDAgs. Notably, none of these novel HDV-like viruses were associated with hepadnavirus infection, supporting the idea that the HDV-HBV association may be specific to humans. Collectively, these data not only broaden our understanding of the diversity and host range of HDV in non-human species, but shed light on its origin and evolutionary history.