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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