Cross-species transmission and evolutionary dynamics of canine distemper virus during a spillover in African lions of Serengeti National Park.

The outcome of pathogen spillover from a reservoir to a novel host population can range from a "dead-end" when there is no onward transmission in the recipient population, to epidemic spread and even establishment in new hosts. Understanding the evolutionary epidemiology of spillover events leading to discrete outcomes in novel hosts is key to predicting risk and can lead to a better understanding of the mechanisms of emergence. Here we use a Bayesian phylodynamic approach to examine cross-species transmission and evolutionary dynamics during a canine distemper virus (CDV) spillover event causing clinical disease and population decline in an African lion population (Panthera leo) in the Serengeti Ecological Region between 1993 and 1994. Using 21 near-complete viral genomes from four species we found that this large-scale outbreak was likely  ignited by a single cross-species spillover event from a canid reservoir to noncanid hosts <1 year before disease detection and explosive spread of CDV in lions. Cross-species transmission from other noncanid species probably fuelled the high prevalence of CDV across spatially structured lion prides. Multiple lines of evidence suggest that spotted hyenas (Crocuta crocuta) could have acted as the proximate source of CDV exposure in lions. We report 13 nucleotide substitutions segregating CDV strains found in canids and noncanids. Our results are consistent with the hypothesis that virus evolution played a role in CDV emergence in noncanid hosts following spillover during the outbreak, suggest that host barriers to clinical infection can limit outcomes of CDV spillover in novel host species.

Identifying Candidate Genetic Markers of CDV Cross-Species Pathogenicity in African Lions.

Canine distemper virus (CDV) is a multi-host pathogen with variable clinical outcomes of infection across and within species. We used whole-genome sequencing (WGS) to search for viral markers correlated with clinical distemper in African lions. To identify candidate markers, we first documented single-nucleotide polymorphisms (SNPs) differentiating CDV strains associated with different clinical outcomes in lions in East Africa. We then conducted evolutionary analyses on WGS from all global CDV lineages to identify loci subject to selection. SNPs that both differentiated East African strains and were under selection were mapped to a phylogenetic tree representing global CDV diversity to assess if candidate markers correlated with documented outbreaks of clinical distemper in lions (n = 3). Of 54 SNPs differentiating East African strains, ten were under positive or episodic diversifying selection and 20 occurred in the clinical strain despite strong purifying selection at those loci. Candidate markers were in functional domains of the RNP complex (n = 19), the matrix protein (n = 4), on CDV glycoproteins (n = 5), and on the V protein (n = 1). We found mutations at two loci in common between sequences from three CDV outbreaks of clinical distemper in African lions; one in the signaling lymphocytic activation molecule receptor (SLAM)-binding region of the hemagglutinin protein and another in the catalytic center of phosphodiester bond formation on the large polymerase protein. These results suggest convergent evolution at these sites may have a functional role in clinical distemper outbreaks in African lions and uncover potential novel barriers to pathogenicity in this species.