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Journal of Virology, April 2006, p. 3912-3922, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.3912-3922.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Function of Bovine CD46 as a Cellular Receptor for Bovine Viral Diarrhea Virus Is Determined by Complement Control Protein 1

Thomas Krey,1,{dagger} Anke Himmelreich,1,{dagger},{ddagger} Manuela Heimann,1 Christian Menge,2 Heinz-Jürgen Thiel,1 Karin Maurer,1 and Till Rümenapf1*

Institut für Virologie, Fachbereich Veterinärmedizin, Justus-Liebig-Universität, Frankfurter Str. 107, 35392 Giessen, Germany,1 Institut für Hygiene und Infektionskrankheiten der Tiere, Fachbereich Veterinärmedizin, Justus-Liebig-Universität, Frankfurter Str. 85-89, 35392 Giessen, Germany2

Received 25 November 2005/ Accepted 5 January 2006

The pestivirus bovine viral diarrhea virus (BVDV) was shown to bind to the bovine CD46 molecule, which subsequently promotes entry of the virus. To assess the receptor usage of BVDV type 1 (BVDV-1) and BVDV-2, 30 BVDV isolates including clinical samples were assayed for their sensitivity to anti-CD46 antibodies. With a single exception the infectivity of all tested strains of BVDV-1 and BVDV-2 was inhibited by anti-CD46 antibodies, which indicates the general usage of CD46 as a BVDV receptor. Molecular analysis of the interaction between CD46 and the BVD virion was performed by mapping the virus binding site on the CD46 molecule. Single complement control protein modules (CCPs) within the bovine CD46 were either deleted or replaced by analogous CCPs of porcine CD46, which does not bind BVDV. While the epitopes recognized by anti-CD46 monoclonal antibodies which block BVDV infection were attributed to CCP1 and CCP2, in functional assays only CCP1 turned out to be essential for BVDV binding and infection. Within CCP1 two short peptides on antiparallel beta strands were identified as crucial for the binding of BVDV. Exchanges of these two peptide sequences were sufficient for a loss of function in bovine CD46 as well as a gain of function in porcine CD46. Determination of the size constraints of CD46 revealed that a minimum length of four CCPs is essential for receptor function. An increase of the distance between the virus binding domain and the plasma membrane by insertion of one to six CCPs of bovine C4 binding protein exhibited only a minor influence on susceptibility to BVDV.

* Corresponding author. Mailing address: Institut für Virologie, Frankfurter Str. 107, D-35392 Giessen, Germany. Phone: 49-641-99-38356. Fax: 49-641-99-38359. E-mail: Till.H.Ruemenapf{at}vetmed.uni-giessen.de.

{dagger} These authors contributed equally to this work.

{ddagger} Present address: Institut für Hygiene und Umwelt, Abteilung Mikrobiologischer Verbraucherschutz, Marckmannstr. 129a, 20539 Hamburg, Germany.

Journal of Virology, April 2006, p. 3912-3922, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.3912-3922.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Krey, T., Moussay, E., Thiel, H.-J., Rumenapf, T. (2006). Role of the Low-Density Lipoprotein Receptor in Entry of Bovine Viral Diarrhea Virus. J. Virol. 80: 10862-10867 [Abstract] [Full Text]  


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