Innate immune basis for rift valley fever susceptibility in mouse models

Lathan, R. , Simon-Chazottes, D., Jouvion, G., Godon, O., Malissen, M., Flamand, M., Bruhns, P. and Panthier, J.-J. (2017) Innate immune basis for rift valley fever susceptibility in mouse models. Scientific Reports, 7, 7096. (doi: 10.1038/s41598-017-07543-8) (PMID:28769107) (PMCID:PMC5541133)

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Abstract

Rift Valley fever virus (RVFV) leads to varied clinical manifestations in animals and in humans that range from moderate fever to fatal illness, suggesting that host immune responses are important determinants of the disease severity. We investigated the immune basis for the extreme susceptibility of MBT/Pas mice that die with mild to acute hepatitis by day 3 post-infection compared to more resistant BALB/cByJ mice that survive up to a week longer. Lower levels of neutrophils observed in the bone marrow and blood of infected MBT/Pas mice are unlikely to be causative of increased RVFV susceptibility as constitutive neutropenia in specific mutant mice did not change survival outcome. However, whereas MBT/Pas mice mounted an earlier inflammatory response accompanied by higher amounts of interferon (IFN)-α in the serum compared to BALB/cByJ mice, they failed to prevent high viral antigen load. Several immunological alterations were uncovered in infected MBT/Pas mice compared to BALB/cByJ mice, including low levels of leukocytes that expressed type I IFN receptor subunit 1 (IFNAR1) in the blood, spleen and liver, delayed leukocyte activation and decreased percentage of IFN-γ-producing leukocytes in the blood. These observations are consistent with the complex mode of inheritance of RVFV susceptibility in genetic studies.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lathan, Dr Rashida
Authors: Lathan, R., Simon-Chazottes, D., Jouvion, G., Godon, O., Malissen, M., Flamand, M., Bruhns, P., and Panthier, J.-J.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN:2045-2322
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Scientific Reports 7: 7096
Publisher Policy:Reproduced under a Creative Commons license

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