{
  "abstract": "Pathogen adaptations to new hosts are central to the disease ecology of cross-species transmission and host switching of viruses. The rabies virus is a model for adaptations to different hosts as it induces behavioral changes that facilitate transmission, while being maintained in distinct species-specific cycles of infection. Here, we demonstrate that the rabies virus requires distinct transmission dynamics in two hosts with different ecologies to establish maintenance, using agent-based modeling, analyses of virus glycoprotein-mediated manipulation of neuroreceptor function, and phylogenetic analysis. Epidemiological models suggest that rabies virus variants adapted to arctic foxes, which sustain rabies virus at very low host densities, require a higher probability of transmission than viruses adapted to raccoons. Using in vitro electrophysiology, we demonstrate that the rabies glycoprotein-derived peptides from arctic fox rabies variants are more potent antagonists of alpha7 nicotinic acetylcholine receptors. These findings suggest a possible functional basis for the behavioral modifications that drive enzootic rabies transmission in the context of host ecology. In addition, a large proportion of residues that may drive rabies virus adaptation to raccoons and arctic foxes are found within this neurotoxin-like region. Furthermore, a residue in the neurotoxin-like region of the mature rabies virus glycoprotein (residue 183) has been associated with pathogenicity, host switching, and disease ecology in previous studies. We propose the hypothesis that rabies virus transmission dynamics adapt to the ecology and physiology of novel hosts through the selection of glycoproteins that elicit specific degrees of behavioral modification and transmission probability.",
  "abstract_shown": true,
  "affiliations": [
    "Département de pathologie et microbiologie, Faculté de médecine vétérinaire, Université de Montréal, Québec J2S 2M2, Canada",
    "Groupe de recherche en épidémiologie des zoonoses et santé publique, University of Montréal, Québec J2S 2M2, Canada",
    "Modelling Hub Division, Applied Public Health Sciences Directorate, Science and Policy Integration Branch, Public Health Agency of Canada, Québec J2S 2M2, Canada",
    "Department of Mathematics and Statistics, University of Alaska Fairbanks, Fairbanks, AK 99775",
    "Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks, AK 99775",
    "Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK 99775",
    "Department of Veterinary Medicine, College of Natural Science and Mathematics, University of Alaska Fairbanks, Fairbanks, AK 99775"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Alice Remal"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Emily S. Acheson"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Patrick A. Leighton"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Erin E. Rees"
    },
    {
      "affs": [
        3
      ],
      "name": "John Rhodes",
      "orcid": "0000-0001-9921-1091"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Brittany C. V. O’Brien"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Maegan M. Weltzin",
      "orcid": "0000-0001-9051-8150"
    },
    {
      "affs": [
        6
      ],
      "name": "Karsten Hueffer",
      "orcid": "0000-0001-7154-9066"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e4tabbm5d2xcj.bib",
  "cited_by": 0,
  "doi": "10.1073/pnas.2618744123",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13715790/",
  "id": "e4tabbm5d2xcj",
  "issns": [
    "0027-8424",
    "1091-6490"
  ],
  "landing_url": "https://doi.org/10.1073/pnas.2618744123",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "423"
    ],
    [
      "heading",
      "Biological Sciences"
    ],
    [
      "heading",
      "Microbiology"
    ],
    [
      "openalex",
      "2406|Rabies epidemiology and control"
    ]
  ],
  "openalex": "W7223232309",
  "pdf_url": null,
  "pmcid": "PMC13715790",
  "pmid": "42911862",
  "published": "2026-10-22",
  "publisher": "National Academy of Sciences",
  "ris": "https://research.draconitic.com/paper/e4tabbm5d2xcj.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:22:59Z",
      "native_id": "PMC13715790",
      "source": "pmc",
      "url": "https://doi.org/10.1073/pnas.2618744123"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "Virus transmission required for maintenance and host adaptation mirrors neurophysiological differences in rabies-derived peptides",
  "title_text": "Virus transmission required for maintenance and host adaptation mirrors neurophysiological differences in rabies-derived peptides",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:59Z",
  "url": "https://research.draconitic.com/paper/e4tabbm5d2xcj",
  "venue": "Proceedings of the National Academy of Sciences of the United States of America",
  "versions": []
}