Human milk mucin inhibits rotavirus replication and prevents experimental gastroenteritis.

Human milk mucin inhibits rotavirus replication and prevents experimental gastroenteritis.
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DOI:
10.1172/jci116078
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发表时间:
1992-11
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
R. Yolken;J. Peterson;S. Vonderfecht;E. Fouts;K. Midthun;D. Newburg
R. Yolken;J. Peterson;S. Vonderfecht;E. Fouts;K. Midthun;D. Newburg
中科院分区:
其他
文献类型:
--
作者:
R. Yolken;J. Peterson;S. Vonderfecht;E. Fouts;K. Midthun;D. Newburg

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由轮状病毒和其他肠道病原体引起的急性胃肠道感染是全世界婴幼儿发病和死亡的主要原因。母乳喂养可以降低婴儿严重胃肠炎的发生率;然而,不同人群对轮状病毒感染的保护程度不同。与牛奶介导的预防病毒性胃肠炎相关的机制尚未完全阐明。我们已经从人乳中分离出了一种大分子成分,它可以抑制组织培养中轮状病毒的复制,并在动物模型系统中预防胃肠炎的发生。组分的纯化表明,抗病毒活性与酸性组分(pI = 4.0-4.6)相关,该组分不含可检测的免疫球蛋白。此外,高水平的抗病毒活性与亲和纯化的人乳粘蛋白复合物相关。粘蛋白复合物的去糖基化导致抗病毒活性的丧失。进一步纯化表明,轮状病毒特异性结合的牛奶粘蛋白复合物,以及46 kD的糖蛋白成分的复合物。唾液酸化学水解后,与46-kD组分的结合大大减少。我们已经证明,人乳粘蛋白可以结合轮状病毒和抑制病毒复制在体外和体内。乳粘蛋白糖蛋白的变化可能与不同水平的抗胃肠道病原体感染的保护有关。
Acute gastrointestinal infections due to rotaviruses and other enteric pathogens are major causes of morbidity and mortality in infants and young children throughout the world. Breast-feeding can reduce the rate of serious gastroenteritis in infants; however, the degrees of protection offered against rotavirus infection vary in different populations. The mechanisms associated with milk-mediated protection against viral gastroenteritis have not been fully elucidated. We have isolated a macromolecular component of human milk that inhibits the replication of rotaviruses in tissue culture and prevents the development of gastroenteritis in an animal model system. Purification of the component indicates that the antiviral activity is associated with an acidic fraction (pI = 4.0-4.6), which is free of detectable immunoglobulins. Furthermore, high levels of antiviral activity are associated with an affinity-purified complex of human milk mucin. Deglycosylation of the mucin complex results in the loss of antiviral activity. Further purification indicated that rotavirus specifically binds to the milk mucin complex as well as to the 46-kD glycoprotein component of the complex. Binding to the 46-kD component was substantially reduced after chemical hydrolysis of sialic acid. We have documented that human milk mucin can bind to rotavirus and inhibit viral replication in vitro and in vivo. Variations in milk mucin glycoproteins may be associated with different levels of protection against infection with gastrointestinal pathogens.