NOTES Glycosylphosphatidylinositol-Anchored CD4/Thy-1 Chimeric Molecules Serve as Human Immunodeficiency Virus Receptors in Human, but Not Mouse, Cells and Are Modulated by Gangliosides

Human and mouse cell lines that expressed a CD4/Thy-l fusion protein on the cell surface were constructed and tested for the capacity to be infected with human immunodeficiency virus. The human cell lines, in contrast to the mouse line, were infectable. The CD4/Thy-l fusion, which is anchored to the membrane by a glycosylphosphatidylinositol tail rather than a peptide linkage, can therefore serve as a human immunodefi-ciency virus receptor. In addition, this molecule, like CD4, is down-modulated in its cell surface expression by exogenous gangliosides. The CD4 glycoprotein is the major cell surface receptor for human immunodeficiency virus (HIV) (22). Its expres-sion on the surface of helper T cells and cells of the monocyte lineage is thought to be the key determinant in HIV tropism and in the immunodeficiency that marks HIV disease. The mechanism of HIV entry into CD4+ cells has not been fully elucidated. It has been clearly established that the first step involves the high-affinity binding of the viral envelope glycoprotein, gpl20, to CD4. The binding site fo