PERSISTENCE OF HIV IN HUMAN INTESTINAL MUCOSA CELLS

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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.