A Mouse Model of Chronic West Nile Virus Disease

PLoS Pathogens

Richard Green¹  Courtney Wilkins¹  Renee C. Ireton¹  Aimee Sekine¹  Kathleen M. Voss¹  Sunil Thomas¹  Martin T. Ferris²  Jennifer M. Lund³  Darla R. Miller³  Michael Mooney³  Shannon McWeeney⁴  Fernando Pardo Manuel de Villena⁴  Michael Gale Jr.⁴  Gabrielle Choonoo⁵  Piper M. Treuting⁵  Jessica B. Graham⁶  Jessica L. Swarts⁶ 

[1] Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, Washington, United States of America;Department of Comparative Medicine, University of Washington, Seattle, Washington, United States of America;Division of Bioinformatics & Computational Biology, Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, Portland, Oregon, United States of America;Lineberger Comprehensive Cancer Center, Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America;OHSU Knight Cancer Center Institute, Oregon Health & Science University, Portland, Oregon, United States of America;Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America

关键词: West Nile virus;    Regulatory T cells;    Mouse models;    Animal models of infection;    Immune response;    Spleen;    Brain diseases;    T cells;   

DOI  :  10.1371/journal.ppat.1005996

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY