title: Characterization of non-lethal West Nile Virus (WNV) infection in horses: Subclinical pathology and innate immune response.
abstract: Most natural West Nile virus (WNV) infections in humans and horses are subclinical or sub-lethal and non-encephalitic. Yet, the main focus of WNV research remains on the pathogenesis of encephalitic disease, mainly conducted in mouse models. We characterized host responses during subclinical WNV infection in horses and compared outcomes with those obtained in a novel rabbit model of subclinical WNV infection (Suen et al. 2015. Pathogens, 4: 529). Experimental infection of 10 horses with the newly emerging WNV-strain, WNVNSW2011, did not result in neurological disease in any animal but transcriptional upregulation of both type I and II interferon (IFN) was seen in peripheral blood leukocytes prior to or at the time of viremia. Likewise, transcript upregulation for IFNs, TNFα, IL1β, CXCL10, TLRs, and MyD88 was detected in lymphoid tissues, while IFNα, CXCL10, TLR3, ISG15 and IRF7 mRNA was upregulated in brains with histopathological evidence of mild encephalitis, but absence of detectable viral RNA or antigen. These responses were reproduced in the New Zealand White rabbits (Oryctolagus cuniculus) experimentally infected with WNVNSW2011,by intradermal footpad inoculation. Kinetics of the anti-WNV antibody response was similar in horses and rabbits, which for both species may be explained by the early IFN and cytokine responses evident in circulating leukocytes and lymphoid organs. Given the similarities to the majority of equine infection outcomes, immunocompetent rabbits appear to represent a valuable small-animal model for investigating aspects of non-lethal WNV infections, notably mechanisms involved in abrogating morbidity.
authors.affiliation: Australian Infectious Diseases Research Centre, University of Queensland, Australia; School of Veterinary Science, University of Queensland, Australia; School of Chemistry and Molecular Biosciences, University of Queensland, Australia. Electronic address: h.bielefeldtohmann1@uq.edu.au.
authors.forename: Helle
authors.initials: H
authors.lastname: Bielefeldt-Ohmann
authors.affiliation: College of Veterinary Medicine & Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Bosco-Lauth
authors.affiliation: College of Veterinary Medicine & Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
authors.forename: Airn-Elizabeth
authors.initials: AE
authors.lastname: Hartwig
authors.affiliation: School of Veterinary Science, University of Queensland, Australia.
authors.forename: M Jasim
authors.initials: MJ
authors.lastname: Uddin
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Australia.
authors.forename: Jean
authors.initials: J
authors.lastname: Barcelon
authors.affiliation: School of Veterinary Science, University of Queensland, Australia.
authors.forename: Willy W
authors.initials: WW
authors.lastname: Suen
authors.affiliation: School of Veterinary Science, University of Queensland, Australia.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Wang
authors.affiliation: Australian Infectious Diseases Research Centre, University of Queensland, Australia; School of Chemistry and Molecular Biosciences, University of Queensland, Australia.
authors.forename: Roy A
authors.initials: RA
authors.lastname: Hall
authors.affiliation: College of Veterinary Medicine & Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bowen
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D006734:Horse Diseases / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D006736:Horses / Q000276:immunology* / Q000821:virology*; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D011817:Rabbits; D014901:West Nile Fever / Q000662:veterinary*; D014902:West Nile virus / Q000276:immunology / Q000302:isolation & purification
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators
keywords: Arbovirus; Equine; Flavivirus; Innate immune response; Interferons