Imperial College London
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Professor Michael A. ("Mike") Skinner

Faculty of Medicine, Department of Infectious Disease

Emeritus Professor in Virology
 
 
 
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Contact

 

+44 (0)20 7594 3938m.skinner Website

 
 
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Assistant

 

Mrs Yasmin Mallu +44 (0)20 7594 3972

 
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Location

 

315Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Buttigieg:2013:10.1128/JVI.02738-12,
author = {Buttigieg, K and Laidlaw, SM and Ross, C and Davies, M and Goodbourn, S and Skinner, MA},
doi = {10.1128/JVI.02738-12},
journal = {Journal of Virology},
title = {Genetic Screen of a Library of Chimeric Poxviruses Identifies an Ankyrin Repeat Protein Involved in Resistance to the Avian Type I Interferon Response},
url = {http://dx.doi.org/10.1128/JVI.02738-12},
volume = {87},
year = {2013}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Viruses must be able to resist host innate responses, especially the type I interferon (IFN) response. They do so by preventing induction or activity of IFN and/or by resisting the antiviral effectors it induces. Poxviruses are no exception, with many mechanisms identified whereby mammalian poxviruses, notably vaccinia (VACV) but also cowpox and myxoma viruses, are able to evade host IFN responses. Similar mechanisms have not been described for avian poxviruses (avipoxviruses). Restricted for permissive replication to avian hosts, they have received less attention; moreover the avian host responses are less well characterised. We show that the prototypic avipoxvirus, fowlpox virus (FWPV) is highly resistant to the antiviral effects of avian IFN. A gain-of-function genetic screen identified fpv014 as contributing to increased resistance to exogenous recombinant chicken IFN-alpha (ChIFN1). Fpv014 is a member of the large family of poxvirus (especially avipoxvirus) genes that encode proteins containing N-terminal ankyrin repeats (ANKs) and C-terminal F-box-like motifs. By binding the Skp1/Cullin-1 complex, the F-box in such proteins appears to target ligands bound by the ANKs for ubiquitination. Mass spectrometry and immunoblotting demonstrated that tandem affinity-purified, tagged fpv014 was complexed with chicken cullin-1 and Skp-1. Prior infection with an fpv014 knockout mutant of FWPV still blocked transfected poly(I:C)-mediated induction of the IFNbeta (ChIFN2) promoter as effectively as parental FWPV, but the mutant was more sensitive to exogenous ChIFN1. Therefore, unlike the related protein fpv012, fpv014 does not contribute to the FWPV block to induction of ChIFN2, but does confer resistance to an established antiviral state.
AU  - Buttigieg,K
AU  - Laidlaw,SM
AU  - Ross,C
AU  - Davies,M
AU  - Goodbourn,S
AU  - Skinner,MA
DO  - 10.1128/JVI.02738-12
PY  - 2013///
SN  - 1098-5514
TI  - Genetic Screen of a Library of Chimeric Poxviruses Identifies an Ankyrin Repeat Protein Involved in Resistance to the Avian Type I Interferon Response
T2  - Journal of Virology
UR  - http://dx.doi.org/10.1128/JVI.02738-12
UR  - http://hdl.handle.net/10044/1/22118
VL  - 87
ER  -
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