INTERFERON-GAMMA DECREASES CELL-SURFACE EXPRESSION OF GALACTOSYL CERAMIDE, THE RECEPTOR FOR HIV-1 GP120 ON HUMAN COLONIC EPITHELIAL-CELLS

HT-29-A7, a CD4-negative clonal derivative of the human colonic adenoc arcinoma cell line HT-29, is particularly sensitive to infection by se veral isolates of HIV-1 and, correspondingly, expresses high amounts o f galactosylceramide (galactocerebroside, GalCer). GalCer is a neutral glycolipid which binds to the HIV-1 envelope glycoprotein gp120 and i s present at abundant levels in normal human epithelial cells of the s mall and large intestine. Treatment of the HT-29-A7 cells with recombi nant gamma-interferon (rIFN gamma) induced a dose-dependent inhibition of GalCer expression on the cell surface, as demonstrated by indirect immunofluorescence and by enzymatic labeling of cell surface glycocon jugates with oxidase-tritiated sodium borohydride. The rIFN gamma effe ct was not associated with any toxicity and was specific for GalCer, s ince expression of carcinoembryonic antigen did not decrease following treatment. The decrease in GalCer expression was associated with resi stance of the cells to HIV-1 infection. In contrast, rIFN gamma did no t alter cell surface expression of CD4, the classical HIV receptor, in HT-29-A7 cells that had been transduced with a retroviral vector expr essing full-length CD4, and there was no effect on their infection. Th ese results strongly suggest that rIFN gamma blocks HIV-1 infection of HT-29-A7 cells by decreasing GalCer synthesis and expression. This ef fect on expression of a viral receptor is a novel antiviral property o f rIFN gamma which should be exploited for antiviral therapeutics. (C) 1994 Academic Press, Inc.