Discovery of a novel Betacoronavirus 1, cpCoV, in goats in China: The new risk of cross-species transmission

Betacoronavirus is a causative agent of respiratory and enteric diseases in humans and animals. Several ruminants are recognized to be intermediate hosts in the transmission of emerging coronaviruses from reservoir hosts to humans. Here, we first report a novel Betacoronavirus isolated from goats suffering from diarrhea in China, putatively named caprine coronavirus (cpCoV). Full-genome characterization and nuclear acid comparisons demonstrated that this virus is an evolutionarily distinct Betacoronavirus belonging to the subgenus Embecovirus and is a Betacoronavirus 1 species. Notably, on phylogenetic trees based on complete genomes and RdRp, S, and N genes, the cpCoVs were grouped into a clade distinct from other Betacoronavirus strains and were closely related to the HKU23- and HKU23-associated coronaviruses. CpCoV possessed a unique genome organization with a truncated NS4a protein and an elongated NS4b protein that showed no significant matches in the GenBank database. The homology of the S and NS4a-4b genes between cpCoV and Embecovirus was less than 95%. Analysis revealed possible recombination events occurred during the evolution of cpCoV and HKU23, and there are striking similarities between the two viruses in evolutionary terms. In addition, cpCoV showed a narrow cell tropism, replicating in human- and bovine-origin cells in vitro, and caused diarrhea and enteric pathologic changes in goats and calves in vivo. We have provided epidemiological, virological, evolutionary, and experimental evidence that cpCoV is a novel etiological agent for enteric disease in goats. Evidently, a spilling-over event might have occurred between ruminants, including goats, camels, cattle, and wild animals. This study highlights the importance of identifying coronavirus diversity and inter-species transmission in ruminants worldwide, broadens our understanding of the ecology of coronaviruses, and aids in the prevention of animal-to-human transmission and outbreaks.