title: Identifying protective host gene expression signatures within the spleen during West Nile virus infection in the collaborative cross model.
abstract: Flaviviruses are hematophagous arthropod-viruses that pose global challenges to human health. Like Zika virus, West Nile Virus (WNV) is a flavivirus for which no approved vaccine exists [1]. The role host genetics play in early detection and response to WNV still remains largely unexplained. In order to capture the impact of genetic variation on innate immune responses, we studied gene expression following WNV infection using the collaborative cross (CC). The CC is a mouse genetics resource composed of hundreds of independently bred, octo-parental recombinant inbred mouse lines [2]. To accurately capture the host immune gene expression signatures of West Nile infection, we used the nanostring platform to evaluate expression in spleen tissue isolated from CC mice infected with WNV over a time course of 4, 7, and 12 days' post-infection [3]. Nanostring is a non-amplification based digital method to quantitate gene expression that uses color-coded molecular barcodes to detect hundreds of transcripts in a sample. Using this approach, we identified unique gene signatures in spleen tissue at days 4, 7, and 12 following WNV infection, which delineated distinct differences between asymptomatic and symptomatic CC lines. We also identified novel immune genes. Data was deposited into the Gene Expression Omnibus under accession GSE86000.
authors.affiliation: Department of Immunology, Center for Innate Immunity and Immune Disease (CIIID), University of Washington, Seattle, Washington, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Green
authors.affiliation: Department of Immunology, Center for Innate Immunity and Immune Disease (CIIID), University of Washington, Seattle, Washington, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Wilkins
authors.affiliation: Department of Immunology, Center for Innate Immunity and Immune Disease (CIIID), University of Washington, Seattle, Washington, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Department of Immunology, Center for Innate Immunity and Immune Disease (CIIID), University of Washington, Seattle, Washington, USA.
authors.forename: Aimee
authors.initials: A
authors.lastname: Sekine
authors.affiliation: Department of Immunology, Center for Innate Immunity and Immune Disease (CIIID), University of Washington, Seattle, Washington, USA.
authors.forename: Renee C
authors.initials: RC
authors.lastname: Ireton
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, North Carolina, USA.
authors.forename: Martin T
authors.initials: MT
authors.lastname: Ferris
authors.affiliation: Department of Immunology, Center for Innate Immunity and Immune Disease (CIIID), University of Washington, Seattle, Washington, USA.
authors.forename: Duncan M
authors.initials: DM
authors.lastname: Hendrick
authors.affiliation: Department of Immunology, Center for Innate Immunity and Immune Disease (CIIID), University of Washington, Seattle, Washington, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Voss
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, North Carolina, USA.
authors.forename: Fernando Pardo-Manuel
authors.initials: FP
authors.lastname: de Villena
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, North Carolina, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Baric
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, North Carolina, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Heise
authors.affiliation: Department of Immunology, Center for Innate Immunity and Immune Disease (CIIID), University of Washington, Seattle, Washington, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Gale
keywords: Collaborative cross; Flaviviruses; Nanostring; Spleen; West Nile virus