PERSISTENCE OF HIV IN HUMAN INTESTINAL MUCOSA CELLS

在最近为检测艾滋病病毒而设计的研究中 感染性，多个连续的人类肿瘤细胞系，只有一个 来自结直肠癌的子集，已被证明 易感(Adachi等人，J.Virol.1987年61：209-213)。这 拟议的项目是对这些观察结果进行跟踪。长期的 这项工作的目标是确定艾滋病毒是否可以在 人结肠或其他胃肠道细胞。具体目标 将是：(1)确定艾滋病毒是否可以在初级或早期复制 正常人小结肠传代细胞或器官培养 肠道和其他GI部位来源；(2)比较HIV的生长情况 在各种原发或早期传代的人类结直肠肿瘤中 和连续的肝癌细胞系；以及(3)使用各种胃肠激素 和其他促进(或抑制)HIV生长的生长因子 正常或恶性细胞。这些研究具有很大的潜力。 对了解艾滋病发病机制具有重要意义。 将采取的方法将包括直接传染性或正常 和恶性胃肠道细胞或器官培养，淋巴细胞生长 HIV，或胃肠道细胞适应的HIV。HIV DNA的转染也将是 用来分析胃肠道细胞的敏感性。病毒的生产将是 使用标准逆转录酶、免疫分析和 原位杂交。多种共育方式将 进行测试，试图扩大病毒产量和/或确定 进行性感染期间的细胞-细胞相互作用。尝试将 使测试培养物的表型特征与 对病毒的相对容许性。在后来的工作中，各种 生长因子，包括胃肠道和其他激素或营养素，将 对其抑制或促进艾滋病毒生长的效果进行测试。 预计该项目取得的成果将不会导致 只是为了更好地了解艾滋病毒感染和疾病 过程，但也可能提出新的治疗方法， 艾滋病的诊断或预防。

In recent studies designed to test the AIDS virus for HIV infectivity, a number of continuous human tumor cell lines, only a subset of those derived from colorectal cancers, proved susceptible (Adachi et al., J. Virol. 61:209-213,1987). This proposed project is to follow up those observation. The long-term objective of the work is to determine if HIV can replicate in human colon or other gastrointestinal cells. The specific aims will be to: (1) determine if HIV can replicate in primary or early passage cell or organ cultures of normal human colon, small intestine, and other GI site origins; (2) compare the growth of HIV in a variety of primary or early passage human colorectal tumors and continuous HCC cell lines; and (3) use various GI hormones and other growth factors to augment (or inhibit) HIV growth in normal or malignant cells. These studies have great potential significance relevant to understanding AIDS pathogenesis. Approaches to be taken will include direct infectivity or normal and malignant GI cell or organ cultures with lymphocyte-grown HIV, or GI cell-adapted HIV. HIV DNA transfection will also be done to analyze suseptibility of GI cells. Virus production will be analyzed using standard reverse transcriptase, immunoassays, and in situ hybridization. A variety of cocultivation methods will be tested in an attempt to amplify virus production and/or to define cell-cell interactions during progressive infections. Attempts will be made to correlate phenotypic features of the test cultures with relative permissiveness for the virus. In later work, a variety of growth factors, including GI and other hormones or nutrients, will be tested for their effects on inhibiting or enhancing HIV growth. It is anticipated that results obtained in this project will lead not only to a better understanding of HIV infection and the disease process, but may also suggest new approaches in therapy, diagnosis or prevention of AIDS.