Giotis, ES;
Laidlaw, SM;
Bidgood, SR;
Albrecht, D;
Burden, JJ;
Robey, RC;
Mercer, J;
(2020)
Modulation of Early Host Innate Immune Response by an Avipox Vaccine Virus' Lateral Body Protein.
Biomedicines
, 8
(12)
, Article 634. 10.3390/biomedicines8120634.
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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.
| Type: | Article |
|---|---|
| Title: | Modulation of Early Host Innate Immune Response by an Avipox Vaccine Virus' Lateral Body Protein |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/biomedicines8120634 |
| Publisher version: | https://doi.org/10.3390/biomedicines8120634 |
| Language: | English |
| Additional information: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | fowlpox virus, interferon, lateral bodies, microarrays, nuclear localisation signal |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10118349 |
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