TY - JOUR
T1 - Octamerization enables soluble CD46 receptor to neutralize measles virus in vitro and in vivo
AU - Christiansen, Dale
AU - Devaux, Patricia
AU - Réveil, Brigitte
AU - Evlashev, Alexey
AU - Horvat, Branka
AU - Lamy, Josette
AU - Rabourdin-Combe, Chantal
AU - Cohen, Jacques H.M.
AU - Gerlier, Denis
PY - 2000
Y1 - 2000
N2 - A chimeric fusion protein encompassing the CD46 ectodomain linked to the C-terminal part of the C4b binding protein (C4bp) α chain (sCD46-C4bpα) 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 sCB46, the octameric sCD46-C4bpα protein was devoid of complement regulatory activity. However, sCB46-C4bpα 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-C4bpα protein was significantly more efficient than monomeric sCD45 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- C4bpα protein, but not the monameric sCD46, fully protected CD46 transgenic mice against a lethal intracranial measles virus challenge.
AB - A chimeric fusion protein encompassing the CD46 ectodomain linked to the C-terminal part of the C4b binding protein (C4bp) α chain (sCD46-C4bpα) 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 sCB46, the octameric sCD46-C4bpα protein was devoid of complement regulatory activity. However, sCB46-C4bpα 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-C4bpα protein was significantly more efficient than monomeric sCD45 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- C4bpα protein, but not the monameric sCD46, fully protected CD46 transgenic mice against a lethal intracranial measles virus challenge.
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U2 - 10.1128/JVI.74.10.4672-4678.2000
DO - 10.1128/JVI.74.10.4672-4678.2000
M3 - Article
C2 - 10775604
AN - SCOPUS:0033997182
SN - 0022-538X
VL - 74
SP - 4672
EP - 4678
JO - Journal of virology
JF - Journal of virology
IS - 10
ER -