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Modulation of Early Host Innate Immune Response by an Avipox Vaccine Virus’ Lateral Body Protein
oleh: Efstathios S. Giotis, Stephen M. Laidlaw, Susanna R. Bidgood, David Albrecht, Jemima J. Burden, Rebecca C. Robey, Jason Mercer, Michael A. Skinner
Format: | Article |
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Diterbitkan: | MDPI AG 2020-12-01 |
Deskripsi
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 <i>FPV184</i>-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 <i>FPV184</i> in FWPVΔ184-infected cells. Ectopic expression of <i>FPV184</i> 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.