NATURE OF INHIBITORS OF HIV IN HUMAN SECRETORY FLUIDS

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征（AIDS）的病原体。 虽然 深入的研究已经指向这种致命的管理， 疾病，迄今为止没有简单的预防和治疗手段， 鉴定 最近，人类唾液被发现可以抑制 HIV-1进入人外周血淋巴细胞，表明唾液和 其它分泌液可能含有具有抗- HIV-1活性。 拟议研究的目的是分离和 确定人体分泌液中的抑制因子，然后研究 这些因素的作用方式，最终目标是发展 艾滋病毒1感染的治疗干预措施。 初步结果 表明人全唾液中高氯酸稳定因子 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 下颌下/舌下唾液）和许多纯化的分泌性唾液（例如唾液分泌物）。 组分（乳铁蛋白，伊加，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 通过许多目前使用的色谱程序进行分馏， 程序的确切顺序取决于分馏模式 抗HIV-1活性。 抗HIV-1抗体的进一步表征 活动将包括确定 对不同病毒分离株和不同靶细胞的活性，以及 确定这些因子是否可以阻止HIV-1形成合胞体， 被感染的细胞 总之，这些研究应该提供有价值的 关于针对HIV-1的人源性武器的性质的信息， 可能导致对HIV-1感染的有效治疗干预。

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.