Interactions between the ectodomains of haemagglutinin and CD46 as a primary step in measles virus entry

Devaux, Patricia; Loveland, Bruce E.; Christiansen, Dale; Milland, Julie; Gerlier, Denis

doi:10.1099/0022-1317-77-7-1477

Cited by 38 publications

(49 citation statements)

References 17 publications

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“…We then measured binding of a soluble form of MV hemagglutinin (sH, Devaux et al, 1996) to mutant and standard CD46 proteins. After normalization for surface expression, the N49Q protein was as efficient as the standard protein in binding (Fig.…”

Section: Relative Orientation Of the Modulesmentioning

confidence: 99%

“…The antiLCD46 monoclonal antibody 20.6 was described by Naniche et al (1993), E4.3 and J4/48 were obtained from Serotec (Oxford, England), and M75 and MI77 were kindly donated by Dr. T. Seya (Seya et al, 1990). Soluble MV hemagglutinin, purified as described by Devaux et al (1996), was kindly donated by D. Gerlier.…”

Section: Viruses Antibodies Soluble MV Hemagglutininmentioning

confidence: 99%

“…Protein analysis was as described (Buchholz et ai., 1996b), by western blotting, fluorescence-activated cell sorter analysis using the appropriate antibodies, or by the cell-cell fusion assay. Binding assays of mutant CD46 proteins to soluble hemagglutinin were according to Devaux et al (1996).…”

Section: Transient Expression Of Mutant Proteinsmentioning

confidence: 99%

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A 3D model for the measles virus receptor CD46 based on homology modeling, Monte Carlo simulations, and hemagglutinin binding studies

et al. 1997

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The two terminal complement control protein (CCP) modules of the CD46 glycoprotein mediate measles virus binding. Three-dimensional models for these two domains were derived based on the NMR structures of two CCP modules of factor H. Both CD46 CCP modules are about 35 8, long, and form a five-stranded antiparallel P-barrel structure. Monte Carlo simulations, sampling the backbone torsion angles of the linker peptide and selecting possible orientations on the basis of minimal solvent-exposed hydrophobic area, were used to predict the orientation of CCP-I relative to CCP-11. We tested this procedure successfully for factor H. For CD46, three clusters of structures differing in the tilt angle of the two domains were obtained. To test these models, we mutagenized the CCP modules. Four proteins, two without an oligosaccharide chain and two with mutated short amino acid segments, reached the cell surface efficiently. Only the protein without the CCP-I oligosaccharide chain maintained binding to the viral attachment protein hemagglutinin. These results are consistent with one of our models and suggest that the viral hemagglutinin does not bind at the membrane-distal tip of CD46, but near the concave CCP-1-11 interface region.

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Section: Relative Orientation Of the Modulesmentioning

confidence: 99%

Section: Viruses Antibodies Soluble MV Hemagglutininmentioning

confidence: 99%

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A 3D model for the measles virus receptor CD46 based on homology modeling, Monte Carlo simulations, and hemagglutinin binding studies

et al. 1997

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“…The identification of cellular receptors used by viruses to enter their host cells has allowed several groups to investigate the potential antivirus properties of recombinant soluble receptors. Whereas recombinant soluble CD4 and Tva exhibited high neutralizing properties, at least in vitro, against human immunodeficiency virus (13,19,27,46) and subgroup A avian sarcoma and leukosis viruses (5,11), respectively, the anti-measles virus (anti-MV) activity of recombinant soluble monomeric CD46 (sCD46) against MV was very poor (16,45). Since MV virus binding and fusion to cells likely involves several CD46 receptor molecules (7), we hypothesized that a multimeric form of soluble CD46 could have more potent antivirus activity.…”

mentioning

confidence: 99%

“…Human CD46 (or membrane cofactor protein), which is expressed on all cells except erythrocytes, is used as a cellular receptor by at least a subgroup of laboratory and wild-type MV strains (17,38; see reference 22 for a review) through the interaction of its ectodomain with that of the MV envelope glycoprotein hemagglutinin (H) (16). This MV H-CD46 interaction induces a multimolecular scaffold in which the MV fusion glycoprotein (F) initiates the fusion between the MV envelope and the plasma cell membrane at a neutral pH (7).…”

mentioning

confidence: 99%

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

Christiansen

Devaux

Réveil

et al. 2000

J Virol

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A chimeric fusion protein encompassing the CD46 ectodomain linked to the C-terminal part of the C4b binding protein (C4bp) ␣ chain (sCD46-C4bp␣) 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-C4bp␣ protein was devoid of complement regulatory activity. However, sCD46-C4bp␣ 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-C4bp␣ 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-C4bp␣ protein, but not the monomeric sCD46, fully protected CD46 transgenic mice against a lethal intracranial measles virus challenge.

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Enhanced MHC class II-restricted presentation of measles virus (MV) hemagglutinin in transgenic mice expressing human MV receptor CD46

et al. 1998

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This study analyzes the role of the measles virus (MV) receptor, i.e. the human CD46 molecule, in the MHC class II-restricted presentation of MV hemagglutinin (H). We generated transgenic mice ubiquitously expressing CD46, with a similar level of transgene expression on the surface of antigen-presenting cells (APC), i.e. B cells, dendritic cells (DC) and macrophages. APC isolated from transgenic mice and nontransgenic controls were tested for their ability to present MV H to H-specific CD4 + I-E d -restricted T cell hybridomas. All three populations of APC were capable of presenting MV to T cell hybridomas, DC being the most efficient. Expression of CD46 on B lymphocytes increased MHC class II-dependent presentation of MV H up to 100-fold, while CD46-transgenic DC stimulated H-specific T cell hybridomas up to 10-fold better than nontransgenic DC. Interestingly, expression of CD46 did not change the presentation efficiency of transgenic macrophages, indicating that CD46-dependent enhancement of antigen presentation depends on the nature of the APC. Furthermore, a single injection of UV-inactivated MV particles into CD46-transgenic mice, but not nontransgenic controls, induced generation of MV-specific T lymphocytes and production of anti-H antibodies, suggesting a role for CD46 in the efficient capture of MV in vivo. These results show for the first time that one ubiquitously expressed cell surface receptor, like CD46, could function in receptor-mediated antigen presentation both in vitro and in vivo and its performance depends on the type of APC which expresses it.

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Interactions between the ectodomains of haemagglutinin and CD46 as a primary step in measles virus entry

Cited by 38 publications

References 17 publications

A 3D model for the measles virus receptor CD46 based on homology modeling, Monte Carlo simulations, and hemagglutinin binding studies

A 3D model for the measles virus receptor CD46 based on homology modeling, Monte Carlo simulations, and hemagglutinin binding studies

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

Enhanced MHC class II-restricted presentation of measles virus (MV) hemagglutinin in transgenic mice expressing human MV receptor CD46

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