Octamerization enables soluble CD46 receptor to neutralize measles virus in vitro and in vivo.
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.
Christiansen
D
D
Immunité et Infections Virales, IVMC, CNRS-UCBL UMR 5537, F-69372 Lyon Cedex 08, France.
Devaux
P
P
Réveil
B
B
Evlashev
A
A
Horvat
B
B
Lamy
J
J
Rabourdin-Combe
C
C
Cohen
J H
JH
Gerlier
D
D
D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016466:CHO Cells; D002459:Cell Fusion; D003167:Complement Activation; D003169:Complement Inactivator Proteins; D006224:Cricetinae; D006023:Glycoproteins; D006389:Hemagglutinins, Viral / Q000378:metabolism; D008457:Measles / Q000517:prevention & control; D008459:Measles virus / Q000276:immunology / Q000378:metabolism*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009500:Neutralization Tests; D011951:Receptors, Complement / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
D000914:Antibodies, Viral; D015703:Antigens, CD; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D006389:Hemagglutinins, Viral; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C032397:hemagglutinin protein G, measles virus