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Journal of Virology, March 2002, p. 2912-2923, Vol. 76, No. 6
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.6.2912-2923.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Myxoma Virus Leukemia-Associated Protein Is Responsible for Major Histocompatibility Complex Class I and Fas-CD95 Down-Regulation and Defines Scrapins, a New Group of Surface Cellular Receptor Abductor Proteins

Jean-Luc Guerin,1 Jacqueline Gelfi,1 Severine Boullier,1 Maxence Delverdier,2 Frederique-Anne Bellanger,1 Stephane Bertagnoli,1 Ingo Drexler,3 Gerd Sutter,3 and Frederique Messud-Petit1*

UMR 960 Microbiologie Moléculaire,1 Laboratoire d'Anatomie-Pathologique, Institut National de la Recherche Agronomique and Ecole Nationale Vétérinaire, 31076 Toulouse, France,2 GSF—Institut für Molekulare Virologie/Institut für Virologie TUM, 81675 Munich, Germany3

Received 18 June 2001/ Accepted 5 December 2001

Down-modulation of major histocompatibility class I (MHC-I) molecules is a viral strategy for survival in the host. Myxoma virus, a member of the Poxviridae family responsible for rabbit myxomatosis, can down-modulate the expression of MHC-I molecules, but the viral factor(s) has not been described. We cloned and characterized a gene coding for an endoplasmic reticulum (ER)-resident protein containing an atypical zinc finger and two transmembrane domains, which we called myxoma virus leukemia-associated protein (MV-LAP). MV-LAP down-regulated surface MHC-I and Fas-CD95 molecules upon transfection; the mechanism probably involves an exacerbation of endocytosis and was lost when the ER retention signal was removed. In addition, the lytic activity of MHC-I-restricted antigen-specific cytolytic T lymphocytes (CTL) against myxoma virus-infected antigen-presenting target cells was significantly reduced, revealing a strong correlation between MHC-I down-regulation by MV-LAP and CTL killing in vitro. In vivo experiments with a knockout virus showed that MV-LAP is a virulence factor, potentially involved in the immunosuppression characteristic of myxomatosis. Data bank analysis revealed that MV-LAP has homologs in herpesviruses and other poxviruses. We propose the name "scrapins" to define a new group of ER-resident surface cellular receptor abductor proteins. The down-regulation of cell surface molecules by scrapins probably helps protect infected cells during viral infections.

* Corresponding author. Mailing address: UMR 960 Microbiologie Moléculaire, Ecole Nationale Vétérinaire, 23, Chemin des Capelles, 31076 Toulouse, Cedex 3, France. Phone: 33 561 19 38 78. Fax: 33 561 19 39 74. E-mail: f.messudpetit{at}envt.fr.

Journal of Virology, March 2002, p. 2912-2923, Vol. 76, No. 6
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.6.2912-2923.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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