Modulation of early host innate immune response by an avipox vaccine virus’ lateral body protein
File(s)
Published version
OA Location
Author(s)
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.
Date Issued
2020-12-19
Date Acceptance
2020-12-16
Citation
Biomedicines, 2020, 8 (12), pp.1-21
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/)
(http://creativecommons.org/licenses/by/4.0/)
License URL
Sponsor
Biotechnology and Biological Sciences Research Council (BBSRC)
Biotechnology and Biological Sciences Research Council (BBSRC)
Biotechnology and Biological Sciences Research Council (BBSRC)
Identifier
https://www.mdpi.com/2227-9059/8/12/634
Grant Number
BBS/B/00115/2
BB/H005323/1
BB/K002465/1
Subjects
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
Date Publish Online
2020-12-19