The essentiality of alpha-2-macroglobulin in human salivary innate immunity against new H1N1 swine origin influenza A virus.

The essentiality of alpha-2-macroglobulin in human salivary innate immunity against new H1N1 swine origin influenza A virus.
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DOI:
10.1002/pmic.200900775
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发表时间:
2010-06
期刊:
影响因子:
3.4
通讯作者:
Huang, Chun-Ming
Huang, Chun-Ming
中科院分区:
生物学3区
文献类型:
--
作者:
Chen, Chao-Hsuan;Zhang, Xing-Quan;Lo, Chih-Wei;Liu, Pei-Feng;Liu, Yu-Tsueng;Gallo, Richard L.;Hsieh, Ming-Fa;Schooley, Robert T.;Huang, Chun-Ming

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2009年春季出现了一种新型甲型H1N1流感病毒株,并在全世界迅速蔓延。虽然最近已经研制出了预期具有保护作用的疫苗,但它们的供应被推迟到流感季节。虽然抗流感药物如神经氨酸酶抑制剂可能是有效的,但对这些药物的耐药性已经有报道。尽管已知人唾液抑制病毒感染并因此可防止病毒传播,但尚未确定负责对流感病毒(特别是甲型流感猪源甲型流感病毒(S-OIV))的这种活性的组分。通过结合结合α 2,6-唾液酸化糖蛋白的珠粒使用蛋白质组学方法,我们确定α-2-巨球蛋白(A2 M)和A2 M样蛋白是唾液先天性免疫抵抗由S-OIV临床分离株介导的血凝的重要组分[San Diego/01/09(SD/H1N1-S-OIV)]。提出了基于A2 M的“双刃剑”对α 2,6-唾液酸化糖蛋白受体的竞争和宿主蛋白酶的失活的模型。我们强调,内源性A2 M在人类先天免疫功能作为一种天然的抑制剂对S-OIV。
A novel strain of influenza A H1N1 emerged in the spring of 2009 and has spread rapidly throughout the world. Although vaccines have recently been developed that are expected to be protective, their availability was delayed until well into the influenza season. While anti-influenza drugs such as neuraminidase inhibitors can be effective, resistance to these drugs has already been reported. Although human saliva was known to inhibit viral infection and may thus prevent viral transmission, the components responsible for this activity on influenza virus, in particular, influenza A swine origin influenza A virus (S-OIV), have not yet been defined. By using a proteomics approach in conjunction with beads that bind alpha 2,6-sialylated glycoprotein, we determined that an alpha-2-macroglobulin (A2M) and a A2M-like protein are essential components in salivary innate immunity against hemagglutination mediated by a clinical isolate of S-OIV [San Diego/01/09 (SD/H1N1-S-OIV)]. A model of an A2M-based “double-edged sword” on competition of alpha 2,6-sialylated glycoprotein receptors and inactivation of host proteases is proposed. We emphasize that endogenous A2M in human innate immunity functions as a natural inhibitor against S-OIV.
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