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

doi:10.1371/journal.ppat.1005996

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

Knight Cancer Institute

Research output: Contribution to journal › Article › peer-review

37 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 language	English (US)
Article number	e1005996
Journal	PLoS pathogens
Volume	12
Issue number	11
DOIs	https://doi.org/10.1371/journal.ppat.1005996
State	Published - Nov 1 2016

ASJC Scopus subject areas

Parasitology
Microbiology
Immunology
Molecular Biology
Genetics
Virology

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Graham, J. B., Swarts, J. L., Wilkins, C., Thomas, S., Green, R., Sekine, A., Voss, K. M., Ireton, R. C., Mooney, M., Choonoo, G., Miller, D. R., Treuting, P. M., Pardo Manuel de Villena, F., Ferris, M. T., McWeeney, S., Gale, M., & Lund, J. M. (2016). A Mouse Model of Chronic West Nile Virus Disease. PLoS pathogens, 12(11), Article e1005996. https://doi.org/10.1371/journal.ppat.1005996

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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.",

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

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AU - Mooney, Michael

AU - Choonoo, Gabrielle

AU - Miller, Darla R.

AU - Treuting, Piper M.

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AU - McWeeney, Shannon

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A Mouse Model of Chronic West Nile Virus Disease

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