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- Title
Modulation of Early Host Innate Immune Response by an Avipox Vaccine Virus' Lateral Body Protein.
- Authors
Giotis, Efstathios S.; Laidlaw, Stephen M.; Bidgood, Susanna R.; Albrecht, David; Burden, Jemima J.; Robey, Rebecca C.; Mercer, Jason; Skinner, Michael A.
- 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.
- Subjects
VACCINE effectiveness; TYPE I interferons; VIRAL vaccines; IMMUNE response; INTERFERON receptors; CYTOSKELETAL proteins
- Publication
Biomedicines, 2020, Vol 8, Issue 12, p634
- ISSN
2227-9059
- Publication type
Article
- DOI
10.3390/biomedicines8120634