A Mouse Model of Chronic West Nile Virus Disease

Jessica B. Graham, Jessica L. Swarts, Courtney Wilkins, Sunil Thomas, Richard Green, Aimee Sekine, Kathleen M. Voss, Renee C. Ireton, Michael Mooney, Gabrielle Choonoo, Darla R. Miller, Piper M. Treuting, Fernando Pardo Manuel de Villena, Martin T. Ferris, Shannon McWeeney, Michael Gale, Jennifer M. Lund

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Infection with West Nile virus (WNV) leads to a range of disease outcomes, including chronic infection, though lack of a robust mouse model of chronic WNV infection has precluded identification of the immune events contributing to persistent infection. Using the Collaborative Cross, a population of recombinant inbred mouse strains with high levels of standing genetic variation, we have identified a mouse model of persistent WNV disease, with persistence of viral loads within the brain. Compared to lines exhibiting no disease or marked disease, the F1 cross CC(032x013)F1 displays a strong immunoregulatory signature upon infection that correlates with restraint of the WNV-directed cytolytic response. We hypothesize that this regulatory T cell response sufficiently restrains the immune response such that a chronic infection can be maintained in the CNS. Use of this new mouse model of chronic neuroinvasive virus will be critical in developing improved strategies to prevent prolonged disease in humans.

Original languageEnglish (US)
Article numbere1005996
JournalPLoS Pathogens
Volume12
Issue number11
DOIs
Publication statusPublished - Nov 1 2016

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Graham, J. B., Swarts, J. L., Wilkins, C., Thomas, S., Green, R., Sekine, A., ... Lund, J. M. (2016). A Mouse Model of Chronic West Nile Virus Disease. PLoS Pathogens, 12(11), [e1005996]. https://doi.org/10.1371/journal.ppat.1005996