A monoclonal antibody that blocks poliovirus attachment recognizes the lymphocyte homing receptor CD44.
A monoclonal antibody, AF3, was previously shown to specifically inhibit poliovirus binding to HeLa cells and to detect a 100-kDa glycoprotein only in cell lines and tissues permissive for poliovirus infection. These results suggested that the 100-kDa protein may be involved in the pathogenesis of poliomyelitis and the cellular function of the poliovirus receptor site. To study further the role of the 100-kDa protein in poliovirus attachment, immunoaffinity purification, amino acid sequencing, and cDNA cloning were undertaken. The results demonstrate that antibody AF3 reacts with the lymphocyte homing receptor CD44, a multifunctional cell surface glycoprotein involved in the homing of circulating lymphocytes to lymph nodes and the modulation of lymphocyte adhesion and activation. Antibody AF3 reacts with a subset of CD44 molecules (AF3CD44H), which appears to be a small fraction of the heterogeneously glycosylated CD44 molecules expressed on hematopoietic and nonhematopoietic cells. Anti-CD44 monoclonal antibodies, previously reported to induce CD44-mediated modulation of lymphocyte activation and adhesion, compete with 125I-AF3 in binding assays, demonstrating functional overlap among the epitopes. The anti-CD44 monoclonal antibody A3D8, which binds to a greater molecular weight range of CD44 than does AF3, inhibits poliovirus binding to a similar degree. CD44 does not act as a poliovirus receptor, since CD44-expressing mouse L-cell transformants did not bind poliovirus. The poliovirus receptor and AF3CD44H may be noncovalently associated, or they may interact through the cytoskeleton or signal transduction pathways.
Shepley
M P
MP
Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Racaniello
V R
VR
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D000914:Antibodies, Viral / Q000276:immunology* / Q000494:pharmacology; D001483:Base Sequence; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D002846:Chromatography, Affinity; D003001:Cloning, Molecular; D000939:Epitopes / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D018960:Hyaluronan Receptors; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D017955:Poliovirus / Q000254:growth & development / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D016201:Receptors, Lymphocyte Homing / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D017421:Sequence Analysis; D014170:Transformation, Genetic; D014779:Virus Replication / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D002352:Carrier Proteins; D000939:Epitopes; D018960:Hyaluronan Receptors; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing