ANTI-VIRAL FACTORS IN HUMAN MILK

轮状病毒及相关病原体引起的胃肠道疾病 对生活在美国的儿童构成严重的健康问题 美国和世界其他地区。母乳喂养已被确认 作为降低相关发病率和死亡率的主要因素 急性腹泻病；然而与此相关的机制 保护措施尚未完全阐明。 我们已经确定了人类乳脂中的一种大分子成分 抑制多种轮状病毒复制的球状颗粒 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 单抗表明活性物质是一种成分。 牛奶粘蛋白复合体的活性，它通过结合到 病毒粒子。用动物模型系统研究的文献表明，口服 服用乳源性糖蛋白可以防止 轮状病毒胃肠炎的发展。 我们提出了一系列实验来提纯和表征 母乳中的抗病毒成分。我们将确定 低聚糖连接，对于抗病毒活性是必不可少的。我们 还将定义作为粘蛋白靶标的病毒表位 有约束力的。我们建议生产大量的牛奶衍生产品 抗病毒因子和活性物质稳定性的确定 在一系列环境条件下。这些研究可能会导致 人乳和乳汁中一种新型抗病毒因子的鉴定 一种新的预防治疗方法的后续发展 以及治疗病毒性胃肠炎。

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.