Whole-Genome-Sequence-Based Evolutionary Analyses of HoBi-like Pestiviruses Reveal Insights into Their Origin and Evolutionary History.

HoBi-like pestivirus (HoBiPeV), classified under Pestivirus H species, is an emerging cattle pathogen of high economic impact. However, the origin and evolution of HoBiPeV are not very clear due to a lack of full genomic sequences from diverse clades. This study aimed to determine full-genome sequences of HoBiPeV strains of three novel clades (c, d and e) and perform full-genome-based genetic and evolutionary analyses. Bayesian phylogenetic analyses herein confirmed the existence and independent evolution of four main HoBiPeV clades (a, c, d and e) globally, with genetic divergence ranging from 13.0% to 18.2%. Our Bayesian molecular clock estimates revealed that HoBiPeV most likely originated in India, with a dated tMRCA of 1938 (1762-2000), evidencing a more recent origin of HoBiPeV. The evolution rate of HoBiPeV was estimated to be 2.133 × 10 -3 subs/site/year at full-genome level but varied widely among individual genes. Selection pressure analyses identified most of the positively selected sites in E2 . Additionally, 21.8% of the ORF codon sites were found under strong episodic diversifying selection, providing first evidence of negative selection in HoBiPeV evolution. No recombination event was evident for HoBiPeV-c, d and e strains. These findings provide new insights into HoBiPeV origin and evolutionary history for better understanding the epidemiology and host-pathogen interactions and stimulate vaccine research.