CD46 Is a Cellular Receptor for Bovine Viral Diarrhea Virus

ABSTRACT Various monoclonal antibodies (MAbs) that recognize cell surface proteins on bovine cells were previously shown to efficiently block infection with bovine viral diarrhea virus (BVDV) (C. Schelp, I. Greiser-Wilke, G. Wolf, M. Beer, V. Moennig, and B. Liess, Arch. Virol. 140:1997-2009, 1995). With one of these MAbs, a 50- to 58-kDa protein was purified from calf thymus by immunoaffinity chromatography. Microchemical analysis of two internal peptides revealed significant sequence homology to porcine and human CD46. The cDNA of bovine CD46 (CD46bov) was cloned and further characterized. Heterologously expressed CD46bov was detected by the MAb used for purification. A putative function of CD46bov as a BVDV receptor was studied with respect to virus binding and susceptibility of nonpermissive cells. While the expression of CD46bov correlated well with the binding of [3H]uridine-labeled BVDV, the susceptibility of cells nonpermissive for BVDV was not observed. However, the expression of CD46bov resulted in a significant increase in the susceptibility of porcine cells to BVDV. These results provide strong evidence that CD46bov serves as a cellular receptor for BVDV.

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Bovine viral diarrhea virus: purification of surface proteins in detergent-containing buffers by fast protein liquid chromatography

Journal of Chromatography A ◽

10.1016/s0021-9673(01)90934-3 ◽

1983 ◽

Vol 266 ◽

pp. 643-649 ◽

Cited By ~ 16

Author(s):

P. Kårsnäs ◽

J. Moreno-Lopez ◽

T. Kristiansen

Keyword(s):

Liquid Chromatography ◽

Bovine Viral Diarrhea Virus ◽

Surface Proteins ◽

Fast Protein Liquid Chromatography ◽

Bovine Viral Diarrhea ◽

Virus Purification ◽

Diarrhea Virus ◽

Viral Diarrhea ◽

Viral Diarrhea Virus

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Faculty Opinions recommendation of CD46 is a cellular receptor for bovine viral diarrhea virus.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1018137.207624 ◽

2004 ◽

Author(s):

John Atkinson

Keyword(s):

Bovine Viral Diarrhea Virus ◽

Bovine Viral Diarrhea ◽

Cellular Receptor ◽

Diarrhea Virus ◽

Viral Diarrhea ◽

Viral Diarrhea Virus

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

Journal of Virology ◽

10.1128/jvi.80.8.3912-3922.2006 ◽

2006 ◽

Vol 80 (8) ◽

pp. 3912-3922 ◽

Cited By ~ 30

Author(s):

Thomas Krey ◽

Anke Himmelreich ◽

Manuela Heimann ◽

Christian Menge ◽

Heinz-Jürgen Thiel ◽

...

Keyword(s):

Bovine Viral Diarrhea Virus ◽

Clinical Samples ◽

Bovine Viral Diarrhea ◽

Minimum Length ◽

Virus Binding ◽

Complement Control Protein ◽

Diarrhea Virus ◽

Viral Diarrhea ◽

Viral Diarrhea Virus ◽

Control Protein

ABSTRACT 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.

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