A Mouse Model of Chronic West Nile Virus Disease.
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.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Jessica B
JB
Graham
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Jessica L
JL
Swarts
Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, Washington, United States of America.
Courtney
C
Wilkins
Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, Washington, United States of America.
Sunil
S
Thomas
Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, Washington, United States of America.
Richard
R
Green
Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, Washington, United States of America.
Aimee
A
Sekine
Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, Washington, United States of America.
Kathleen M
KM
Voss
Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, Washington, United States of America.
Renee C
http://orcid.org/0000-0002-5844-9981
RC
Ireton
Division of Bioinformatics & Computational Biology, Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon, United States of America.|OHSU Knight Cancer Center Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
Michael
M
Mooney
Division of Bioinformatics & Computational Biology, Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon, United States of America.|OHSU Knight Cancer Center Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
Gabrielle
G
Choonoo
Lineberger Comprehensive Cancer Center, Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Darla R
DR
Miller
Department of Comparative Medicine, University of Washington, Seattle, Washington, United States of America.
Piper M
http://orcid.org/0000-0002-1812-1519
PM
Treuting
Lineberger Comprehensive Cancer Center, Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Fernando
F
Pardo Manuel de Villena
Lineberger Comprehensive Cancer Center, Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Martin T
http://orcid.org/0000-0003-1241-6268
MT
Ferris
Division of Bioinformatics & Computational Biology, Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon, United States of America.|OHSU Knight Cancer Center Institute, Oregon Health & Science University, Portland, Oregon, United States of America.|Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
Shannon
http://orcid.org/0000-0001-8333-6607
S
McWeeney
Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, Washington, United States of America.
Michael
M
Gale
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.|Department of Global Health, University of Washington, Seattle, Washington, United States of America.
Jennifer M
http://orcid.org/0000-0003-3284-979X
JM
Lund
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014901:West Nile Fever / Q000276:immunology*; D014902:West Nile virus / Q000276:immunology