PERSISTENCE OF HIV IN HUMAN INTESTINAL MUCOSA CELLS

在最近的艾滋病病毒检测研究中 感染性，一些连续的人类肿瘤细胞系，只有一个 来自结直肠癌的那些子集，证明 易感的（阿达奇等人，J. Virol. 61：209- 213，1987）。 这 拟议项目是对这些意见采取后续行动。 长期 这项工作的目的是确定艾滋病毒是否可以在 人结肠或其它胃肠道细胞。 具体目标 将：（1）确定艾滋病毒是否可以在原发性或早期复制 正常人结肠的传代细胞或器官培养物，小 肠和其他GI部位起源;（2）比较HIV的生长 在多种原发性或早期传代人结肠直肠肿瘤中 和连续的HCC细胞系;和（3）使用各种GI激素 和其他生长因子，以增加（或抑制）艾滋病毒的生长， 正常或恶性细胞。 这些研究有很大的潜力 对了解艾滋病发病机制具有重要意义。 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与淋巴细胞生长 HIV或GI细胞适应的HIV。 HIV DNA转染也将是 用来分析胃肠道细胞的易感性。 病毒生产将是 使用标准逆转录酶、免疫测定和 原位杂交 将采用多种共培养方法， 测试以试图扩增病毒产生和/或确定 进行性感染期间的细胞间相互作用。 尝试将 使测试培养物的表型特征与 对病毒的相对宽容。 在后来的工作中，各种 生长因子，包括GI和其他激素或营养素， 测试其抑制或增强HIV生长的效果。 预计该项目所取得的成果将导致 只有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， 诊断或预防艾滋病。

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.