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.
Highlights
West Nile virus (WNV) is an emerging flavivirus, and a potential model pathogen for other viruses in its genus such as Zika, dengue, and yellow fever viruses
Much experimental work has been directed at understanding the host immune response to flavivirus infections such as West Nile virus (WNV) using mouse models of infection
As part of a screen of more than 100 RIX lines from the Collaborative Cross (CC) for unique disease outcomes resulting from West Nile virus infection, we identified CC(032x013)F1 as having a unique course of disease following WNV infection
Summary
West Nile virus (WNV) is an emerging flavivirus, and a potential model pathogen for other viruses in its genus such as Zika, dengue, and yellow fever viruses. Since its introduction to North America in 1999, West Nile virus has spread throughout the USA to cause significant morbidity and mortality in the Western hemisphere as well as worldwide. It is predicted that WNV and other flaviviruses will continue to cause a significant disease burden to the global population, with expansion possible as mosquito habitats expand and bird migration patterns change with continued shifts in climate worldwide. WNV is neuroinvasive and can cause disease ranging from self-limiting febrile illness to disease of the central nervous system (CNS), including meningitis and encephalitis [1]. Most knowledge of anti-WNV immunity comes from study of WNV infection using inbred mouse models of infection, generally using C57BL/6J (B6) mice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
