Preliminary studies by us have shown that some human colon carcinoma cell lines are susceptible to infection by the human immunodeficiency virus (HIV). In addition, these cell lines and normal colon mucosa express RNA for the HIV receptor (CD4). These findings have significant implications for one possible mode of entry, spread and replication of HIV. We plan to assess the biologic mechanisms that may be involved. We plan to carry out systematic studies on numerous colon cancer lines for the CD4 receptor using immunohistochemistry, immunoprecipitation, Northern blots and in situ hybridization. We will study the biological/functional activity of the CD4 receptor and assess the role of epithelial cell polarity by examining the membrane distribution (brush border vs. basolateral membranes) for the CD4 receptor. These studies will also be carried out on primary cultures of human fetal colon cells. We will also perform studies on pinch biopsies of colon from patients with AIDS and AIDS Related Complex (ARC). Finally, we are able to prepare transplants from human fetal colon to the back of nude mice. These transplants can be injected with HIV and after different times, the transplants will be studied for HIV uptake, replication and syncytia formation.
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