Global transmission, spatial segregation, and recombination determine the long-term evolution and epidemiology of bovine coronaviruses

Abstract

Bovine coronavirus (BCoV) iswidespread in cattle andwild ruminant populations throughout theworld. The virus causes neonatal calf diarrhea andwinter dysentery in adult cattle, aswell as upper and lower respiratory tract infection in young cattle. We isolated and deep sequenced whole genomes of BCoV fromcalveswith respiratory distress in the south-west of France and conducted a comparative genome analysis using globally collected BCoV sequences to provide insights into the genomic characteristics, evolutionary origins, and global diversity of BCoV.Molecular clock analyses allowed us to estimate that the BCoV ancestor emerged in the 1940s, and that two geographically distinct lineages diverged from the 1960s-1970s. A recombination event in the spike gene (breakpoint at nt 1100) may be at the origin of the genetic divergence sixty years ago. Little evidence of genetic mixing between the spatially segregated lineages was found, suggesting that BCoV genetic diversity is a result of a global transmission pathway that occurred during the last century. However, we found variation in evolution rates between the European and non-European lineages indicating differences in virus ecology.