The stronger downregulation of in vitro and in vivo innate antiviral responses by a very virulent strain of Infectious Bursal Disease Virus (IBDV), compared to a classical strain, is mediated, in part, by the VP4 protein
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Author(s)
Type
Journal Article
Abstract
IBDV is economically important to the poultry industry. Very virulent (vv) strains cause higher mortality rates than other strains for reasons that remain poorly understood. In order to provide more information on IBDV disease outcome, groups of chickens (n = 18) were inoculated with the vv strain, UK661, or the classical strain, F52/70. Birds infected with UK661 had a lower survival rate (50%) compared to F52/70 (80%). There was no difference in peak viral replication in the bursa of Fabricius (BF), but the expression of chicken IFNα, IFNβ, MX1, and IL-8 was significantly lower in the BF of birds infected with UK661 compared to F52/70 (p < 0.05) as quantified by RTqPCR, and this trend was also observed in DT40 cells infected with UK661 or F52/70 (p < 0.05). The induction of expression of type I IFN in DF-1 cells stimulated with polyI:C (measured by an IFN-β luciferase reporter assay) was significantly reduced in cells expressing ectopic VP4 from UK661 (p < 0.05), but was higher in cells expressing ectopic VP4 from F52/70. Cells infected with a chimeric recombinant IBDV carrying the UK661-VP4 gene in the background of PBG98, an attenuated vaccine strain that induces high levels of innate responses (PBG98-VP4UK661) also showed a reduced level of IFNα and IL-8 compared to cells infected with a chimeric virus carrying the F52/70-VP4 gene (PBG98-VP4F52/70) (p < 0.01), and birds infected with PBG98-VP4UK661 also had a reduced expression of IFNα in the BF compared to birds infected with PBG98-VP4F52/70 (p < 0.05). Taken together, these data demonstrate that UK661 induced the expression of lower levels of anti-viral type I IFN and proinflammatory genes than the classical strain in vitro and in vivo and this was, in part, due to strain-dependent differences in the VP4 protein.
Date Issued
2020-06-09
Date Acceptance
2020-05-25
Citation
Frontiers in Cellular and Infection Microbiology, 2020, 10
ISSN
2235-2988
Publisher
Frontiers Media
Start Page
315
Journal / Book Title
Frontiers in Cellular and Infection Microbiology
Volume
10
Copyright Statement
Copyright © 2020 Dulwich, Asfor, Gray, Giotis, Skinner and Broadbent. This is an
open-access article distributed under the terms of the Creative Commons Attribution
License (CC BY). The use, distribution or reproduction in other forums is permitted,
provided the original author(s) and the copyright owner(s) are credited and that the
original publication in this journal is cited, in accordance with accepted academic
practice. No use, distribution or reproduction is permitted which does not comply
with these terms.
open-access article distributed under the terms of the Creative Commons Attribution
License (CC BY). The use, distribution or reproduction in other forums is permitted,
provided the original author(s) and the copyright owner(s) are credited and that the
original publication in this journal is cited, in accordance with accepted academic
practice. No use, distribution or reproduction is permitted which does not comply
with these terms.
Sponsor
Biotechnology and Biological Sciences Research Council (BBSRC)
National Centre for the Replacement, Refinement and Reduction of Animals in Research
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/32582573
Grant Number
BB/K002465/1
NC/R001138/1
Subjects
IBDV
VP4
cytokines
inflammation
type I IFN
virulence
Publication Status
Published
Coverage Spatial
Switzerland
Article Number
ARTN 315