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M148R and M149R are two virulence factors for myxoma virus pathogenesis in the European rabbit

Blanié, Sophie and Mortier, Jérémy and Delverdier, Maxence and Bertagnoli, Stéphane and Camus-Bouclainville, Christelle M148R and M149R are two virulence factors for myxoma virus pathogenesis in the European rabbit. (2009) Veterinary Research, vol. 4 (n° 1). ISSN 0928-4249

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Official URL: http://dx.doi.org/10.1051/vetres:2008049

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). MYXV has a linear double-stranded DNA genome that encodes several factors important for evasion from the host immune system. Among them, four ankyrin (ANK) repeat proteins were identified: M148R, M149R, M150R and M-T5. To date, only M150R and M-T5 were studied and characterized as critical virulence factors. This article presents the first characterization of M148R and M149R. GFP fusions allowed us to localize them in a viral context. Whereas M149R is only cytoplasmic, interestingly, M148R is in part located in the nucleolus, a unique feature for an ANK repeat poxviral protein. In order to evaluate their implication in viral pathogenicity, targeted M148R, M149R, or both deletions were constructed in the wild type T1 strain of myxoma virus. In vitro infection of rabbit and primate cultured cells as well as primary rabbit cells allowed us to conclude that M148R and M149R are not likely to be implicated in cell tropism or host range functions. However, in vivo experiments revealed that they are virulence factors since after infection of European rabbits with mutant viruses, a delay in the onset of clinical signs, an increase of survival time and a dramatic decrease in mortality rate were observed. Moreover, histological analysis suggests that M148R plays a role in the subversion of host inflammatory response by MYXV.

Item Type:Article
Additional Information:Thanks to EDP Sciences editor. The original article is available at http://tinyurl.com/39h8jwx
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:French research institutions > Institut National de la Recherche Agronomique - INRA
Université de Toulouse > Ecole Nationale Vétérinaire de Toulouse - ENVT
Laboratory name:
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Deposited By: Christelle Camus-Bouclainville
Deposited On:03 Jun 2010 13:35

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