Adenovirus type 5 fiber knob binds to MHC class I alpha2 domain at the surface of human epithelial and B lymphoblastoid cells.
Adenovirus serotype 5 (Ad5) fiber receptor was investigated using reverse antibody biopanning of a phage-displayed hexapeptide library, and virus-neutralizing monoclonal antibodies (mAbs 1D6.3 and 7A2.7) raised against recombinant Ad5 fiber knob. Both mAbs inhibited attachment of Ad5 to HeLa cells. Mimotopes of 1D6.3 showed homology with the C-terminal segment of the alpha2 domain of the heavy chain of human MHC class I molecules (MHC-I alpha2), and mimotopes of 7A2.7 were consensus to human fibronectin type III (FNIII) modules. In vitro, GST-fused MHC-I alpha2- and FNIII-derived oligopeptides interacted with recombinant fibers in a subgroup-specific manner. In vivo, the MHC-I alpha2 synthetic icosapeptide RAIVGFRVQWLRRYFVNGSR showed a net neutralization effect on Ad5 in HeLa cells, whereas the FNIII icosapeptide RHILWTPANTPAMGYLARVS significantly increased Ad5 binding to HeLa cells. Daudi cells, which lack surface expression of HLA class I molecules, showed a weak capacity for Ad5 binding. In beta2-microglobulin-transfected Daudi cells, Ad5 attachment and permissivity were restored to HeLa cell levels, with 4000 receptors per cell and a binding constant of 1.4x10(10)/M. The results suggested that the conserved region of MHC-I alpha2-domain including Trp167 represents a high affinity receptor for Ad5 fiber knob, whereas ubiquitous FNIII modules would serve as auxiliary receptors.
Hong
S S
SS
Laboratoire de Virologie et Pathogénèse Moléculaires (CNRS URA 1487),Institut de Biologie, Faculté de Médecine, Montpellier, France.
Karayan
L
L
Tournier
J
J
Curiel
D T
DT
Boulanger
P A
PA
D000260:Adenoviruses, Human / Q000378:metabolism*; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology*; D001435:Bacteriophages; D001665:Binding Sites; D001667:Binding, Competitive; D002213:Capsid / Q000378:metabolism*; D036022:Capsid Proteins; D004848:Epithelium / Q000378:metabolism / Q000821:virology; D005353:Fibronectins / Q000276:immunology; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D019151:Peptide Library; D011991:Receptors, Virus / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D014162:Transfection; D015678:Viral Structural Proteins; D001613:beta 2-Microglobulin / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D036022:Capsid Proteins; D005353:Fibronectins; D015395:Histocompatibility Antigens Class I; D019151:Peptide Library; D011991:Receptors, Virus; D011994:Recombinant Proteins; D015678:Viral Structural Proteins; C085301:adenovirus receptor; D001613:beta 2-Microglobulin; C018315:hexon capsid protein, Adenovirus