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Modulation of early host innate immune response by an avipox vaccine virus’ lateral body protein

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Title: Modulation of early host innate immune response by an avipox vaccine virus’ lateral body protein
Authors: Giotis, E
Laidlaw, S
Bidgood, S
Albrecht, D
Burden, J
Robey, R
Mercer, J
Skinner, M
Item Type: Journal Article
Abstract: The avian pathogen fowlpox virus (FWPV) has been successfully used as a vaccine vector in poultry and humans, but relatively little is known about its ability to modulate host antiviral immune responses in these hosts, which are replication-permissive and nonpermissive, respectively. FWPV is highly resistant to avian type I interferon (IFN) and able to completely block the host IFN-response. Microarray screening of host IFN-regulated gene expression in cells infected with 59 different, nonessential FWPV gene knockout mutants revealed that FPV184 confers immunomodulatory capacity. We report that the FPV184-knockout virus (FWPVΔ184) induces the cellular IFN response as early as 2 h postinfection. The wild-type, uninduced phenotype can be rescued by transient expression of FPV184 in FWPVΔ184-infected cells. Ectopic expression of FPV184 inhibited polyI:C activation of the chicken IFN-β promoter and IFN-α activation of the chicken Mx1 promoter. Confocal and correlative super-resolution light and electron microscopy demonstrated that FPV184 has a functional nuclear localisation signal domain and is packaged in the lateral bodies of the virions. Taken together, these results provide a paradigm for a late poxvirus structural protein packaged in the lateral bodies, capable of suppressing IFN induction early during the next round of infection.
Issue Date: 19-Dec-2020
Date of Acceptance: 16-Dec-2020
URI: http://hdl.handle.net/10044/1/85101
DOI: 10.3390/biomedicines8120634
ISSN: 2227-9059
Publisher: MDPI
Start Page: 1
End Page: 21
Journal / Book Title: Biomedicines
Volume: 8
Issue: 12
Copyright Statement: © 2020 by the authors. Submitted for possible open access publication under the termsand conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Biotechnology and Biological Sciences Research Council (BBSRC)
Biotechnology and Biological Sciences Research Council (BBSRC)
Funder's Grant Number: BBS/B/00115/2
BB/H005323/1
BB/K002465/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Pharmacology & Pharmacy
Research & Experimental Medicine
fowlpox virus
interferon
lateral bodies
nuclear localisation signal
microarrays
HERPES-SIMPLEX-VIRUS
FOWLPOX-VIRUS
TRANSCRIPTION FACTORS
GENETIC SCREEN
REPLICATION
INTERFERON
CELLS
ACTIVATION
EVASION
SUBUNIT
fowlpox virus
interferon
lateral bodies
microarrays
nuclear localisation signal
Publication Status: Published
Open Access location: https://www.mdpi.com/2227-9059/8/12/634/pdf
Online Publication Date: 2020-12-19
Appears in Collections:Department of Infectious Diseases
Faculty of Medicine



This item is licensed under a Creative Commons License Creative Commons