Stimulation of human natural interferon-alpha response via paramyxovirus hemagglutinin lectin-cell interaction.
A lectin-carbohydrate recognition event without enzymatic function is proposed as molecular basis for an important innate immune response to enveloped viruses. It involves the hemagglutinin-neuraminidase (HN) glycoprotein of Newcastle disease virus (NDV) and sialic acid expressing cellular receptors on human natural interferon (IFN) alpha producing cells. This conclusion is based on two types of experimental evidence: (a) strong UV irradiation of NDV, which destroyed the cell binding and hemadsorption (HAd) but not the neuraminidase (NA) activity of HN, also destroyed its IFN-alpha inducing activity; (b) DNA transfectants expressing HN mutant molecules with greatly reduced NA but not HAd activity induced IFN-alpha while transfectants expressing HN mutant molecules with greatly reduced NA and HAd activity were incapabable of inducing IFN-alpha in human peripheral blood mononuclear cells. The results clarify molecular mechanisms involved in pattern recognition during innate immune responses.
Division of Cellular Immunology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Jinyang
J
Zeng
Philippe
P
Fournier
Volker
V
Schirrmacher
D000327:Adsorption; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D005434:Flow Cytometry; D015707:HN Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009522:Newcastle disease virus / Q000378:metabolism / Q000528:radiation effects; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D018108:Respirovirus / Q000276:immunology / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism; D014466:Ultraviolet Rays
D015707:HN Protein; D016898:Interferon-alpha; D011956:Receptors, Cell Surface; D012794:Sialic Acids