Zeng Jinyang, Fournier Philippe, Schirrmacher Volker
Division of Cellular Immunology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
J Mol Med (Berl). 2002 Jul;80(7):443-51. doi: 10.1007/s00109-002-0339-1. Epub 2002 May 7.
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.
一种无酶功能的凝集素-碳水化合物识别事件被认为是对包膜病毒重要天然免疫反应的分子基础。它涉及新城疫病毒(NDV)的血凝素-神经氨酸酶(HN)糖蛋白以及人天然干扰素(IFN)α产生细胞上表达唾液酸的细胞受体。这一结论基于两类实验证据:(a)对NDV进行强紫外线照射,破坏了细胞结合和血细胞吸附(HAd),但未破坏HN的神经氨酸酶(NA)活性,同时也破坏了其诱导IFN-α的活性;(b)表达NA活性大幅降低但HAd活性未受影响的HN突变分子的DNA转染子可诱导IFN-α,而表达NA和HAd活性均大幅降低的HN突变分子的转染子则无法在人外周血单核细胞中诱导IFN-α。这些结果阐明了天然免疫反应中模式识别所涉及的分子机制。