Human immunodeficiency virus infection is efficiently mediated by a glycolipid-anchored form of CD4.
Two broad roles have been revealed for the CD4 molecule. It serves as a receptor for both class II major histocompatibility complex molecules and human immunodeficiency virus (HIV). Upon binding class II major histocompatibility molecules, CD4 functions to enhance T-cell activation. By binding to CD4, HIV gains entry into the cell. We have used a chimeric molecule of CD4 and lymphocyte function-associated antigen 3 (LFA-3), CD4PI, which lacks a membrane-spanning domain and is instead anchored in the membrane by linkage to glycosyl-phosphatidylinositol. To further define the structural attributes of viral receptors, and specifically those of CD4 required for HIV infection, we have expressed CD4PI and CD4 in a human T-cell line, HSB-2. We find that CD4PI is able to mediate infection of these cells by HIV with similar, if not greater efficiency, compared with wild-type CD4. Thus the membrane-spanning region of CD4 is not required for HIV infection, and a lipid-anchored protein can serve as a viral receptor.
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Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115.
Finberg
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R
Chaudhuri
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Sleckman
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BP
Burakoff
S J
SJ
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis / Q000235:genetics; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006017:Glycolipids / Q000502:physiology*; D017261:Glycosylphosphatidylinositols; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000502:physiology*; D012190:Retroviridae / Q000235:genetics; D013601:T-Lymphocytes
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D006017:Glycolipids; D017261:Glycosylphosphatidylinositols; D007140:Immunoglobulin Fab Fragments; D010716:Phosphatidylinositols