ANTI-VIRAL FACTORS IN HUMAN MILK

母乳中的抗病毒因子

• 批准号: 2201708
• 负责人: ROBERT H YOLKEN
• 金额: $ 22.08万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/2201708
• 关键词: Rotavirus; affinity chromatography; animal tissue; antiviral agents; biological products; chemical stability; developmental nutrition; disease /disorder model; drug resistance; epitope mapping; gastroenteritis; glycoproteins; human milk; human tissue; ion exchange chromatography; laboratory mouse; mucins; nutrition related tag; oligosaccharides; protein purification; tissue resource /registry; virion

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.

由轮状病毒和相关剂引起的胃肠道疾病 对于居住在曼联的儿童来说构成严重的健康问题 国家和世界其他地区。 已经确定了母乳喂养 是降低发病率和死亡率相关的主要因素 患有急性腹泻病；但是与此相关的机制 保护尚未完全阐明。 我们已经确定了人奶脂的大分子成分 抑制各种轮状病毒的复制的球 菌株。 抗病毒活性与酸性糖蛋白有关 不包含免疫球蛋白的分数。 反应性 单克隆抗体表明活性材料是一种成分 牛奶粘蛋白复合物的作用，并通过与 病毒体。 使用动物模型系统的研究证明了口头 牛奶来源的糖蛋白可以防止 轮状病毒胃肠炎的发育。 我们提出了一系列实验，以净化和表征 人乳的抗病毒成分。 我们将确定 对于抗病毒活性至关重要的寡糖连接。 我们 还将定义为粘蛋白靶标的病毒表位 结合。我们建议产生大量的牛奶来源 抗病毒因子并确定活性材料的稳定性 在一系列环境条件下。 这些研究可能导致 鉴定人类牛奶中新型的抗病毒因子和 随后开发一种新的治疗方式，以预防 和病毒胃肠炎的治疗。