Hepatovirus infections in juvenile seals from the North Sea

The discovery of several novel hepatovirus species in marine and terrestrial mammals has expanded the recognised members of the genus Hepatovirus and has provided better understanding on the evolutionary origins of human hepatovirus A (HAV). Using high throughput sequencing we detected a seal hepatovirus (SealHAV_NL/PV/21), in liver tissue of a deceased harbor seal (Phoca vitulina) originating from the Dutch North Sea coast. RT-PCR screening of liver samples of 88 harbor seals and 12 grey seals (Halichoerus grypus) from the same region identified seal hepatovirus in nine juvenile harbor seals in which minor sequence variation was observed in the VP1 gene. Whole-genome sequence analysis showed that SealHAV_NL/PV/21 displayed 95.6% nucleotide indentity to New England seal hepatovirus but had a 5'-UTR which contained additional 51 bp. Phylogenetic analysis showed that seal hepatoviruses clustered in a monophyletic group separate from other hepatovirus species that have been identified in terrestrial mammals. Assessment of seal hepatovirus RNA loads in organs of all infected animals showed that the liver had the highest number of RNA copies with up to 10⁷ RNA copies per mg of tissue. Seal hepatovirus RNA was readily detected by in situ hybridization in hepatocytes in the liver but was not associated with pathological lesions. Serological screening of 90 contemporary seal sera using a HAV-based ELISA showed the presence of hepatovirus antibodies in 14 harbor seals and one juvenile grey seal. These findings collectively show that seal hepatovirus is enzootic among seals of the North Sea, causing quiescent infections in young animals.