The role of a mechanistic host in maintaining arctic rabies variant distributions: Assessment of functional genetic diversity in Alaskan red fox (Vulpes vulpes)

PLoS One. 2021 Apr 8;16(4):e0249176. doi: 10.1371/journal.pone.0249176. eCollection 2021.

Abstract

Populations are exposed to different types and strains of pathogens across heterogeneous landscapes, where local interactions between host and pathogen may present reciprocal selective forces leading to correlated patterns of spatial genetic structure. Understanding these coevolutionary patterns provides insight into mechanisms of disease spread and maintenance. Arctic rabies (AR) is a lethal disease with viral variants that occupy distinct geographic distributions across North America and Europe. Red fox (Vulpes vulpes) are a highly susceptible AR host, whose range overlaps both geographically distinct AR strains and regions where AR is absent. It is unclear if genetic structure exists among red fox populations relative to the presence/absence of AR or the spatial distribution of AR variants. Acquiring these data may enhance our understanding of the role of red fox in AR maintenance/spread and inform disease control strategies. Using a genotyping-by-sequencing assay targeting 116 genomic regions of immunogenetic relevance, we screened for sequence variation among red fox populations from Alaska and an outgroup from Ontario, including areas with different AR variants, and regions where the disease was absent. Presumed neutral SNP data from the assay found negligible levels of neutral genetic structure among Alaskan populations. The immunogenetically-associated data identified 30 outlier SNPs supporting weak to moderate genetic structure between regions with and without AR in Alaska. The outliers included SNPs with the potential to cause missense mutations within several toll-like receptor genes that have been associated with AR outcome. In contrast, there was a lack of genetic structure between regions with different AR variants. Combined, we interpret these data to suggest red fox populations respond differently to the presence of AR, but not AR variants. This research increases our understanding of AR dynamics in the Arctic, where host/disease patterns are undergoing flux in a rapidly changing Arctic landscape, including the continued northward expansion of red fox into regions previously predominated by the arctic fox (Vulpes lagopus).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alaska
  • Animal Diseases / epidemiology
  • Animal Diseases / genetics
  • Animal Diseases / virology
  • Animal Distribution
  • Animals
  • Foxes / genetics*
  • Foxes / virology
  • Haplotypes
  • Mutation, Missense
  • Ontario
  • Polymorphism, Single Nucleotide*
  • Rabies / epidemiology
  • Rabies / genetics*
  • Rabies / virology
  • Rabies virus / isolation & purification
  • Rabies virus / pathogenicity
  • Toll-Like Receptors / genetics

Substances

  • Toll-Like Receptors

Grants and funding

This research was funded by a Natural Sciences and Engineering Research Council Discovery Grant to CJK (PGPIN2016- 05373). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This research was enabled in part by support provided by Compute Canada (www.computecanada.ca; RRG gme-665-ab).