Characterization of a Novel Hepadnavirus in the White Sucker (Catostomus commersonii) from the Great Lakes Region of the United States

Abstract

The white sucker Catostomus commersonii is a freshwater teleost often utilized as a resident sentinel. Here, we sequenced the full genome of a hepatitis B-like virus that infects white suckers from the Great Lakes Region of the United States. Dideoxy sequencing confirmed that the white sucker hepatitis B virus (WSHBV) has a circular genome (3,542 bp) with the prototypical codon organization of hepadnaviruses. Electron microscopy demonstrated that complete virions of approximately 40 nm were present in the plasma of infected fish. Compared to avi- and orthohepadnaviruses, sequence conservation of the core, polymerase, and surface proteins was low and ranged from 16 to 27% at the amino acid level. An X protein homologue common to the orthohepadnaviruses was not present. The WSHBV genome included an atypical, presumptively noncoding region absent in previously described hepadnaviruses. Phylogenetic analyses confirmed WSHBV as distinct from previously documented hepadnaviruses. The level of divergence in protein sequences between WSHBV and other hepadnaviruses and the identification of an HBV-like sequence in an African cichlid provide evidence that a novel genus of the family Hepadnaviridae may need to be established that includes these hepatitis B-like viruses in fishes. Viral transcription was observed in 9.5% (16 of 169) of white suckers evaluated. The prevalence of hepatic tumors in these fish was 4.9%, and only 2.4% of fish were positive for both virus and hepatic tumors. These results are not sufficient to draw inferences regarding the association of WSHBV and carcinogenesis in white sucker.IMPORTANCE We report the first full-length genome of a hepadnavirus from fishes. Phylogenetic analysis of this genome indicates divergence from genomes of previously described hepadnaviruses from mammalian and avian hosts and supports the creation of a novel genus. The discovery of this novel virus may better our understanding of the evolutionary history of hepatitis B-like viruses of other hosts. In fishes, knowledge of this virus may provide insight regarding possible risk factors associated with hepatic neoplasia in the white sucker. This may also offer another model system for mechanistic research.

Distinct Viral Lineages from Fish and Amphibians Reveal the Complex Evolutionary History of Hepadnaviruses

“…A hepadnaviruslike sequence was also identified from the transcriptome data set of the African cichlid Ophthalmotilapia ventralis (GenBank accession number JL559376) (16,38). Notably, this is the only hepadnaviral sequence in the entire 454 pyrosequencing transcriptome of O. ventralis, comprising the polymerase polyprotein (Fig.…”

“…Avian and reptile endogenous hepadnaviruses have been described previously (14,(17)(18)(19). The fish WSHBV was described in a concurrent study (16). …”

“…Liver pathology is less commonly induced by avihepadnaviruses, although duck hepatitis B virus (DHBV) can cause liver necrosis (9). The first hepadnavirus from a bony fish, the white sucker (Catostomus commersonii), class Actinopterygii, was described in 2015, although no disease association was ob-served (16). To date, no exogenous reptilian or amphibian hepadnaviruses have been reported.…”

Evolutionary biology of human hepatitis viruses

“…33 Endogenous and exogenous viruses distantly related to HBV were detected in reptiles, fish and amphibians. [34][35][36][37] HCV-related viruses were detected in horses in 2012, and evidence for sporadic spill-over infections of the horse-associated viruses into dogs and donkeys was found. [38][39][40][41] Soon afterwards, highly diverse HCV-related viruses were detected in bats and rodents, 42,43 in cattle, 44,45 and in black-and-white colobus monkeys.…”

Molecular characterization of a novel orthomyxovirus from rainbow and steelhead trout (Oncorhynchus mykiss)

“…The supernate was clarified further by centrifugation at 12,000 × g for 30 min at 4 • C using an SW 50.1 rotor (Beckman) and the virus pelleted by additional centrifugation through a 200 L sucrose (30% w/v) cushion at 77,000 × g for 1.5 h at 4 • C using the SW 50.1 rotor. The virus pellet was resuspended in 50 L of distilled water and prepared for electron microscopy of negatively stained virions (Hahn et al, 2015). All grids were examined using a JEOL 1400 transmission electron microscope.…”