Identifying candidate genetic markers of cdv cross-species pathogenicity in African lions

Julie K. Weckworth, Brian W. Davis, Melody E. Roelke-Parker, Rebecca P. Wilkes, Craig Packer, Ernest Eblate, Michael K. Schwartz, L. Scott Mills

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number872
Pages (from-to)1-23
Number of pages23
JournalPathogens
Volume9
Issue number11
DOIs
StatePublished - Nov 2020

Bibliographical note

Funding Information:
Funding: This study was funded by the Morris Animal Foundation through grant ID D14ZO‐013, “Understanding spillover of a deadly virus in a well‐studied African lion population”. Further financial support was provided by the National Science Foundation Graduate Research Fellowship under Grant #DGE‐0809127, the National Science Foundation grant #DGE‐0504628, North Carolina State University, and the University of Montana.

Keywords

  • African lion
  • Canine distemper virus
  • Cross-species pathogenicity
  • Evolutionary genetics
  • Multi-host pathogen
  • Spillover
  • Viral genomics

PubMed: MeSH publication types

  • Journal Article

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