Senecavirus cetus a novel picornavirus isolated from cetaceans represents a major host switching to the marine environment.

Senecavirus A (SVA), an emerging virus that causes vesicular disease in swine, was, until recently, the only member of the Senecavirus genus (Picornaviridae). Here, we report the isolation and complete genome sequence of two isolates of cetacean picornavirus 1 (Senecavirus cetus), a novel picornavirus species of the Senecavirus genus from dead stranded cetaceans from Alaska. One isolate was from a harbor porpoise stranded in 2017, and another from a beluga whale, stranded in 2019. Whole-genome sequencing of Senecavirus cetus strains showed a genome-wide nucleotide identity of 98.8% and a genome size of 7455 nucleotides. The Senecavirus cetus genomes are most similar to SVA with a 58.3% genome-wide pairwise nucleotide identity. Infection of eleven available cell lines from terrestrial and aquatic animals showed that beluga and sheep cells were susceptible to infection by Senecavirus cetus. Phylogenetic and ancestral state reconstruction analyses supported the novel virus being a member of the Senecavirus genus and provided the first evidence of Senecavirus-like picornavirus infecting marine mammals and likely descending from a terrestrial host ancestor. These discoveries provided important information on the evolutionary relationships and taxonomy of picornaviruses and increased our understanding of the genomic characteristics and potential host range of Senecavirus cetus.