Avian influenza virus (A/H3N8) with a putative mammalian-adaptive mutation found in a stranded grey seal pup (Halichoerus grypus) rescued on the Cornwall coast, UK

Avian Influenza A Viruses (IAV) in different species of seals display a spectrum of pathogenicity, from subclinical infection to unusual mortality events. In this report, we describe a case of avian IAV infection in a 3-4 month old grey seal (Halichoerus grypus) pup, rescued from St Michaels Mount, Cornwall in 2017. The pup underwent medical treatment, but died after two weeks. Post-mortem examination and histology indicated sepsis as the cause of death.nnIAV NP antigen was detected by immunohistochemistry in the nasal mucosa only, with no evidence of pathology. Sensitive real-time reverse transcription polymerase chain reaction assays detected trace amounts of viral RNA within the lower respiratory tract, suggesting that the infection may have been cleared naturally. IAV infection prevalence among grey seals might therefore be underestimated. In addition, the fact that the animal was rescued and entered into contact with humans raised concerns about potential zoonotic risk. Nucleotide sequencing revealed the virus to be IAV subtype H3N8. Combining a GISAID database BLAST search and time-scaled phylogenetic analyses, we inferred that the seal infection came from an unsampled, locally circulating (in Northern Europe) source viruses, likely originally derived from wild Anseriformes, which may or may not have been circulating in seals. From examining the protein alignments, we found several residue changes in the seal virus that did not occur in the bird viruses, including D701N in the PB2 segment, a rare mutation, and a hallmark of mammalian adaptation of bird viruses, which has been reported in another IAV H3N8 avian-to-seal transmission event. IAVs of H3N8 subtype have been noted for their particular ability to cross the species barrier and cause productive infections, including historical records suggesting that they may have caused the 1889 pandemic. Therefore, infections such as the one we report here may be of interest to pandemic surveillance and risk, and may help us better understand the determinants and drivers of mammalian adaptation in influenza.