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) ex chain (sCD46-C4bp alpha) 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-C46p alpha protein was devoid of complement regulatory activity. However. sCD36-C4bp alpha 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-C46p alpha 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 alpha protein, but not the monomeric sCD46, fully protected CD46 transgenic mice against a lethal intracranial measles virus challenge.