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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK040620-02
Application #
3241020
Study Section
Diabetes and Digestive and Kidney Diseases Special Grants Review Committee (DDK)
Project Start
1988-07-15
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Lage, J M; Weinberg, D S; Yavner, D L et al. (1989) The biology of tetraploid hydatidiform moles: histopathology, cytogenetics, and flow cytometry. Hum Pathol 20:419-25