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Journal of Virology, March 2004, p. 2510-2516, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2510-2516.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

A Virulence Factor of Myxoma Virus Colocalizes with NF-{kappa}B in the Nucleus and Interferes with Inflammation

Christelle Camus-Bouclainville,1 Laurence Fiette,2 Sophie Bouchiha,2 Béatrice Pignolet,1 Dorian Counor,1 Cédric Filipe,1 Jacqueline Gelfi,1 and Frédérique Messud-Petit1*

UMR 1225 Interactions Hôtes Agents Pathogènes, INRA/ENVT, Ecole Nationale Vétérinaire de Toulouse, 31076 Toulouse Cedex,1 Unité d'Histopathologie, Institut Pasteur, 75724 Paris Cedex 15, France2

Received 4 August 2003/ Accepted 3 November 2003

NF-{kappa}B is one of the most important elements that coordinate stress-induced, immune, and inflammatory responses. Myxoma virus, a member of the Poxviridae family responsible for rabbit myxomatosis, codes for several factors that help its survival in the host. In this study, we focused on the product of the M150R gene. We show that the protein has nine ankyrin repeats (ANKs), with the eighth having a close similarity with the nuclear localization signal-containing ANK of I-{kappa}B{alpha}, which regulates NF-{kappa}B activity by sequestering it in the cytosol. Because the viral protein is targeted to the nucleus, it was named MNF, for myxoma nuclear factor. This localization was lost when the eighth ANK was removed. In tumor necrosis factor alpha-treated cells, MNF and NF-{kappa}B colocalized as dotted spots in the nucleus. In vivo experiments with a knockout virus showed that MNF is a critical virulence factor, with its deletion generating an almost apathogenic virus. Detailed histological examinations revealed an increase in the inflammatory process in the absence of MNF, consistent with the interference of MNF with the NF-{kappa}B-induced proinflammatory pathway. Because MNF has homologs in other poxviruses, such as vaccinia, cowpox, and variola viruses, this protein is probably part of a key mechanism that contributes to the immunogenic and pathogenic properties of these viruses.

* Corresponding author. Mailing address: UMR 1225, Ecole Nationale Vétérinaire de Toulouse, 23 chemin des Capelles, 31076 Toulouse Cedex, France. Phone: (33) 561-19-38-78. Fax: (33) 561-19-39-74. E-mail: f.messudpetit{at}envt.fr.

Journal of Virology, March 2004, p. 2510-2516, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2510-2516.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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