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MNF, an ankyrin repeat protein of myxoma virus, is part of a native cellular SCF complex during viral infection

Blanié, Sophie and Gelfi, Jacqueline and Bertagnoli, Stéphane and Camus-Bouclainville, Christelle MNF, an ankyrin repeat protein of myxoma virus, is part of a native cellular SCF complex during viral infection. (2010) Virology Journal , vol.7 (n°56). ISSN 1743-422X

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Official URL: http://dx.doi.org/10.1186/1743-422X-7-56

Abstract

Myxoma virus (MYXV), a member of the Poxviridae family, is the agent responsible for myxomatosis, a fatal disease in the European rabbit (Oryctolagus cuniculus). Like all poxviruses, MYXV is known for encoding multiple proteins that regulate cellular signaling pathways. Among them, four proteins share the same ANK/PRANC structure: M148R, M149R, MNF (Myxoma Nuclear factor) and M-T5, all of them described as virulence factors. This family of poxvirus proteins, recently identified, has drawn considerable attention for its potential role in modulating the host ubiquitin-proteasome system during viral infection. To date, many members of this novel protein family have been shown to interact with SCF components, in vitro. Here, we focus on MNF gene, which has been shown to express a nuclear protein presenting nine ANK repeats, one of which has been identified as a nuclear localization signal. In transfection, MNF has been shown to colocalise with the transcription factor NF-!B in the nucleus of TNFa-stimulated cells. Functionally, MNF is a critical virulence factor since its deletion generates an almost apathogenic virus. In this study, to pursue the investigation of proteins interacting with MNF and of its mechanism of action, we engineered a recombinant MYXV expressing a GFP-linked MNF under the control of MNF native promoter. Infection of rabbits with MYXV-GFPMNF recombinant virus provided the evidence that the GFP fusion does not disturb the main function of MNF. Hence, cells were infected with MYXV-GFPMNF and immunoprecipitation of the GFPMNF fusion protein was performed to identify MNF’s partners. For the first time, endogenous components of SCF (Cullin-1 and Skp1) were co-precipitated with an ANK myxoma virus protein, expressed in an infectious context, and without over-expression of any protein.

Item Type:Article
Additional Information:Thanks to BioMed Central editor. The definitive version is available at http://www.virologyj.com/ The original PDF of the article can be found at : http://www.virologyj.com/content/7/1/56
Audience (journal):International peer-reviewed journal
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Institution: Université de Toulouse > Ecole Nationale Vétérinaire de Toulouse - ENVT
French research institutions > Institut National de la Recherche Agronomique - INRA
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Deposited By:SYLVIE OUDDANE

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