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Modulation of Early Host Innate Immune Response by an Avipox Vaccine Virus’ Lateral Body Protein

Giotis, Efstathios S and Laidlaw, Stephen M and Bidgood, Susanna R and Albrecht, David and Burden, Jemima J and Robey, Rebecca C and Mercer, Jason and Skinner, Michael A (2020) 'Modulation of Early Host Innate Immune Response by an Avipox Vaccine Virus’ Lateral Body Protein.' Biomedicines, 8 (12). p. 634. ISSN 2227-9059

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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.

Item Type: Article
Uncontrolled Keywords: fowlpox virus; interferon; lateral bodies; nuclear localisation signal; microarrays
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 08 Jan 2021 11:49
Last Modified: 06 Jan 2022 14:20

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