Hemagglutinin protein of wild-type measles virus activates toll-like receptor 2 signaling.
Pattern recognition via Toll-like receptors (TLR) by antigen-presenting cells is an important element of innate immunity. We report that wild-type measles virus but not vaccine strains activate cells via both human and murine TLR2, and this is a property of the hemagglutinin (H) protein. The ability to activate cells via TLR2 by wild-type MV H protein is abolished by mutation of a single amino acid, asparagine at position 481 to tyrosine, as is found in attenuated strains, which is important for interaction with CD46, the receptor for these strains. TLR2 activation by MV wild-type H protein stimulates induction of proinflammatory cytokines such as interleukin-6 (IL-6) in human monocytic cells and surface expression of CD150, the receptor for all MV strains. Confirming the specificity of this interaction, wild-type H protein did not induce IL-6 release in macrophages from TLR2-/- mice. Thus, the unique property of MV wild-type strains to activate TLR2-dependent signals might essentially contribute not only to immune activation but also to viral spread and pathogenicity by upregulating the MV receptor on monocytes.
Bieback
Karen
K
Institute for Virology and Immunobiology, University of Würzburg, D-97078 Würzburg, Germany.
Lien
Egil
E
Klagge
Ingo M
IM
Avota
Elita
E
Schneider-Schaulies
Jürgen
J
Duprex
W Paul
WP
Wagner
Herrmann
H
Kirschning
Carsten J
CJ
Ter Meulen
Volker
V
Schneider-Schaulies
Sibylle
S
D019943:Amino Acid Substitution; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D029721:Drosophila Proteins; D005786:Gene Expression Regulation / Q000276:immunology; D006389:Hemagglutinins, Viral / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008458:Measles Vaccine; D008459:Measles virus / Q000235:genetics / Q000276:immunology*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014613:Vaccines, Attenuated
D015703:Antigens, CD; C497857:CD46 protein, human; D029721:Drosophila Proteins; D006389:Hemagglutinins, Viral; D015850:Interleukin-6; C497859:Mcp protein, mouse; D008458:Measles Vaccine; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014613:Vaccines, Attenuated; C032397:hemagglutinin protein G, measles virus