ANTI-VIRAL FACTORS IN HUMAN MILK

母乳中的抗病毒因子

基本信息

批准号：
2201707
负责人：
ROBERT H YOLKEN
金额：
$ 21.07万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-05-01 至 1997-04-30
项目状态：
已结题

项目摘要

Gastrointestinal diseases caused by rotaviruses and related agents constitute serious health problems for children living in the United States and other areas of the world. Breast feeding has been identified as a major factor in decreasing the morbidity and mortality associated with acute diarrheal disease; however the mechanisms associated with this protection have not been fully elucidated. We have identified a macromolecular component of the human milk fat globule which inhibits the replication of a wide range of rotavirus strains. The anti-viral activity is associated with acidic glycoprotein fractions which do not contain immunoglobulins. Reactivity with monoclonal antibodies indicates that the active material is a component of the milk mucin complex and that it exerts its activity by binding to virions. Studies with an animal model system document that the oral administration of the milk-derived glycoprotein can prevent the development of rotavirus gastroenteritis. We propose a series of experiments to purify and characterize the anti-viral component of human milk. We will determine the oligosaccharide linkages which are essential for anti-viral activity. We will also define the viral epitopes which are the targets of the mucin binding. we propose to generate large amounts of the milk-derived anti-viral factor and determine the stability of the active material under a range of environmental conditions. These studies may result in the identification of a novel anti-viral factor in human milk and in the subsequent development of a new therapeutic modality for the prevention and treatment of viral gastroenteritis.

轮状病毒及相关病原体引起的胃肠道疾病对居住在美国的儿童构成严重的健康问题各州和世界其他地区。已确定母乳喂养是降低相关发病率和死亡率的一个主要因素患有急性腹泻病；然而与此相关的机制保护尚未完全阐明。我们已经鉴定出人乳脂肪的大分子成分抑制多种轮状病毒复制的小球菌株。抗病毒活性与酸性糖蛋白有关不含免疫球蛋白的级分。反应性与单克隆抗体表明活性物质是一种成分乳粘蛋白复合物，它通过结合来发挥其活性病毒体。动物模型系统研究表明，口腔给予乳源性糖蛋白可以预防轮状病毒胃肠炎的发展。我们提出了一系列实验来纯化和表征母乳中的抗病毒成分。我们将确定寡糖连接对于抗病毒活性至关重要。我们还将定义作为粘蛋白目标的病毒表位绑定。我们建议生产大量的牛奶衍生产品抗病毒因子并测定活性物质的稳定性在一系列环境条件下。这些研究可能会导致在母乳和牛奶中鉴定出一种新型抗病毒因子随后开发了一种新的预防治疗方式以及病毒性胃肠炎的治疗。