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@article{Laidlaw:2013:10.1128/JVI.02736-12,
author = {Laidlaw, SM and Robey, R and Davies, M and Giotis, E and Ross, C and Buttigieg, K and Goodbourn, S and Skinner, MA},
doi = {10.1128/JVI.02736-12},
journal = {Journal of Virology},
title = {Genetic Screen of a Mutant Poxvirus Library Identifies an Ankyrin Repeat Protein Involved in Blocking Induction of Avian Type I Interferon},
url = {http://dx.doi.org/10.1128/JVI.02736-12},
volume = {87},
year = {2013}
}

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TY  - JOUR
AB  - Mammalian poxviruses, including vaccinia virus (VACV), have evolved multiple mechanisms to evade the host type I interferon (IFN) responses at different levels, with viral proteins targeting IFN induction, signaling and antiviral effector functions. Avian poxviruses (avipoxviruses), which have been developed as recombinant vaccine vectors for permissive (i.e. poultry) and non-permissive (i.e. mammals, including humans) species, encode no obvious equivalents of any of these proteins. We show that fowlpox virus (FWPV) fails to induce chicken IFN-beta (ChIFN2) and is able to block its induction by transfected poly(I:C), an analog of cytoplasmic double-strand (ds) RNA. A broad-scale loss-of-function genetic screen was used to find FWPV-encoded modulators of poly(I:C)-mediated ChIFN2 induction. It identified fpv012, a member of a family of poxvirus genes, highly expanded in the avipoxviruses (31 in FWPV; 51 in canarypox virus (CNPV), representing 15% of the total gene complement), encoding proteins containing N-terminal ankyrin repeats (ANKs) and C-terminal F-box-like motifs. Under ectopic expression, the first ANK of fpv012 is dispensable for inhibitory activity and the CNPV ortholog is also able to inhibit induction of ChIFN2. FWPV defective in fpv012 replicate well in culture and barely induce ChIFN2 during infection, suggesting other factors are involved in blocking IFN induction and resisting the antiviral effectors. Nevertheless, unlike parental and revertant viruses, the mutants induce moderate levels of expression of interferon stimulated genes (ISG), suggesting either that there is sufficient ChIFN2 expression to partially induce the ISGs or the involvement of alternative, IFN-independent pathways, that are also normally blocked by fpv012.
AU  - Laidlaw,SM
AU  - Robey,R
AU  - Davies,M
AU  - Giotis,E
AU  - Ross,C
AU  - Buttigieg,K
AU  - Goodbourn,S
AU  - Skinner,MA
DO  - 10.1128/JVI.02736-12
PY  - 2013///
SN  - 1098-5514
TI  - Genetic Screen of a Mutant Poxvirus Library Identifies an Ankyrin Repeat Protein Involved in Blocking Induction of Avian Type I Interferon
T2  - Journal of Virology
UR  - http://dx.doi.org/10.1128/JVI.02736-12
UR  - http://hdl.handle.net/10044/1/22046
VL  - 87
ER  -

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