NATURE OF INHIBITORS OF HIV IN HUMAN SECRETORY FLUIDS

人体分泌液中 HIV 抑制剂的性质

• 批准号: 2130631
• 负责人: JOSEPH M KINKADE
• 金额: $ 16.85万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-05-15 至 1995-05-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2130631
• 关键词: agglutinins; antiviral agents; bioassay; chromatography; human immunodeficiency virus 1; human milk; human tissue; immunoglobulin A; lactoferrin; lysozyme; peroxidases; physical separation; polymerase chain reaction; protease inhibitor; saliva; tear; virus infection mechanism; virus replication

The human immunodeficiency virus type 1 (HIV-1) has been defined as the etiologic agent of he acquired immune deficiency syndrome (AIDS). Although intensive research has been directed toward management of this lethal disease, to date no facile means of prevention and treatment has been identified. Recently, human saliva was found to inhibit the infectivity of HIV-1 into human peripheral blood lymphocytes, suggesting that saliva and possibly other secretory fluids contain human-derived products having anti- HIV-1 activity. The objective of the proposed study is to isolate and identify the inhibitory factors in human secretory fluids and to then study the modes of action of these factors, with the ultimate goal of developing therapeutic interventions against HIV-1 infection. Preliminary results indicate that perchloric acid-stable factors(s) in human whole saliva inhibit the infectivity of HIV-1, as judged by the inhibition of expression of reverse transcriptase activity released into the extracellular milieu of HIV-1 infected CEM cells. Proposed studies will include screening of various secretory fluids (milk, tears, whole saliva, parotid saliva, and submandibular/sublingual saliva) and of a number of purified secretory components (lactoferrin, IgA, lactoferrin-IgA complexes, lysozyme, peroxidase, agglutinins and secretory leukocyte protease inhibitor) for anti-HIV-1 activity. Concomitantly, native secretory fluids will be fractionated by a number of currently used chromatographic procedures, with the exact sequence of procedures dependent upon the fractionation patterns of the anti-HIV-1 activities. Further characterization of the anti-HIV-1 activities will include determination of the specificities of the activities toward different virus isolates and different target cells, and determination if the factors can prevent syncytia formation by HIV-1- infected cells. Together, these studies should provide valuable information regarding the nature of human-derived weapons against HIV-1 and may lead to effective therapeutic intervention of HIV-1 infections.

人类免疫缺陷病毒 1 型（HIV-1）被定义为 获得性免疫缺陷综合症（艾滋病）的病原体。 虽然 深入的研究已针对这种致命的管理 该病至今尚无简便的预防和治疗方法 确定。 最近，人们发现人类唾液可以抑制病毒的传染性。 HIV-1 进入人外周血淋巴细胞，表明唾液和 可能其他分泌液含有具有抗- HIV-1 活性。 拟议研究的目的是分离和 识别人体分泌液中的抑制因子并进行研究 这些因素的作用方式，最终目标是发展 针对 HIV-1 感染的治疗干预措施。 初步结果 表明人类全唾液中的高氯酸稳定因子 抑制 HIV-1 的感染性，通过抑制表达来判断 释放到细胞外环境的逆转录酶活性 HIV-1 感染的 CEM 细胞。 拟议的研究将包括筛选 各种分泌液（乳汁、泪液、全唾液、腮腺唾液和 颌下/舌下唾液）和许多纯化的分泌物 成分（乳铁蛋白、IgA、乳铁蛋白-IgA 复合物、溶菌酶、 过氧化物酶、凝集素和分泌性白细胞蛋白酶抑制剂） 抗 HIV-1 活性。 与此同时，天然分泌液将 通过许多当前使用的色谱程序进行分级， 程序的确切顺序取决于分馏模式 抗 HIV-1 活性。 抗 HIV-1 的进一步表征 活动将包括确定 针对不同病毒分离株和不同靶细胞的活性，以及 确定这些因素是否可以阻止 HIV-1- 合胞体的形成 被感染的细胞。 总之，这些研究应该提供有价值的 有关针对 HIV-1 的人源武器性质的信息以及 可能导致 HIV-1 感染的有效治疗干预。