National Academy of Sciences, Proceedings of the National Academy of Sciences, 22(115), 2018
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Significance Coronaviruses exhibit a propensity for interspecies transmission, with SARS- and MERS-coronaviruses as notable examples. Cross-species transmission by coronaviruses is foremost determined by the virus’ ability to bind receptors of new hosts. We here report that the recently identified, yet globally distributed porcine deltacoronavirus employs host aminopeptidase N (APN) as an entry receptor via S protein-mediated interaction with an interspecies conserved domain that allows for APN orthologue-mediated entry. Identification of APN as a deltacoronavirus receptor emphasizes the remarkable preferential employment of cell surface host peptidases as receptors by coronaviruses. Our findings provide important insight into how receptor usage of coronaviruses may fuel cross-host transmission between distantly related species and necessitate surveillance studies of deltacoronaviruses in thus far unappreciated potential reservoirs, including humans.