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Journal of Virology, May 2000, p. 4672-4678, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Octamerization Enables Soluble CD46 Receptor To Neutralize Measles Virus In Vitro and In Vivo

Dale Christiansen,1 Patricia Devaux,1 Brigitte Réveil,2 Alexey Evlashev,3 Branka Horvat,3 Josette Lamy,4 Chantal Rabourdin-Combe,3 Jacques H. M. Cohen,2 and Denis Gerlier1,*

Immunité et Infections Virales, IVMC, CNRS-UCBL UMR 5537, F-69372 Lyon Cedex 08,1 Laboratoire d'Immunologie, Pôle Biomolécules IFR 53, UFR Médecine URCA, F-51100 Reims,2 Immunobiologie Fondamentale et Clinique, INSERM U 503, ENS Lyon, F-69364 Lyon Cedex 07,3 and Laboratoire des Protéines Complexes, Université François Rabelais, F-37032 Tours Cedex,4 France

Received 20 September 1999/Accepted 15 February 2000

A chimeric fusion protein encompassing the CD46 ectodomain linked to the C-terminal part of the C4b binding protein (C4bp) alpha  chain (sCD46-C4bpalpha ) was produced in eukaryotic cells. This protein, secreted as a disulfide-linked homo-octamer, was recognized by a panel of anti-CD46 antibodies with varying avidities. Unlike monomeric sCD46, the octameric sCD46-C4bpalpha protein was devoid of complement regulatory activity. However, sCD46-C4bpalpha was able to bind to the measles virus hemagglutinin protein expressed on murine cells with a higher avidity than soluble monomeric sCD46. Moreover, the octameric sCD46-C4bpalpha protein was significantly more efficient than monomeric sCD46 in inhibiting virus binding to CD46, in blocking virus induced cell-cell fusion, and in neutralizing measles virus in vitro. In addition, the octameric sCD46-C4bpalpha protein, but not the monomeric sCD46, fully protected CD46 transgenic mice against a lethal intracranial measles virus challenge.

* Corresponding author. Mailing address: Immunité et Infections Virales, IVMC, CNRS-UCBL UMR 5537, F-69372 Lyon Cedex 08, France. Phone: 33 4 78 77 86 18. Fax: 33 4 78 77 87 54. E-mail: gerlier{at}laennec.univ-lyon1.fr.

Journal of Virology, May 2000, p. 4672-4678, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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