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

Autor: Efstathios S. Giotis, Stephen M. Laidlaw, Susanna R. Bidgood, David Albrecht, Jemima J. Burden, Rebecca C. Robey, Jason Mercer, Michael A. Skinner
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Biomedicines, Vol 8, Iss 12, p 634 (2020)
Druh dokumentu: article
ISSN: 2227-9059
DOI: 10.3390/biomedicines8120634
Popis: 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.
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