DETERMINATION OF THE ROLE FOR CD21 DURING EPSTEIN-BARR-VIRUS INFECTION OF B-LYMPHOBLASTOID CELLS

Epstein-Barr virus (EBV), a herpesvirus with oncogenic potential, is c amouflaged with glycoprotein 350/220, which mimics the human ligand C3 dg and thereby binds to and exploits complement receptor type 2 (CR2; CD21), the EBV receptor. It has not been possible to determine the rol e of CR2 during postbinding events of viral infection because all B ly mphocytes express endogenous CR2, precluding an informative study of r eceptor mutants. We have overcome this obstacle through creation of a novel experimental system based on molecular dissection of the ligand- binding domains of human CR2 and murine CR2. Our results demonstrate f irst, that two discontinuous amino acid substitutions within the ligan d-binding domain of murine CR2 render it capable of mediating EBV infe ction of human B-lymphoblastoid cells, and second, that the specific r ole of CR2 during EBV infection is to capture virions at the cell surf ace, after which cofactors not associated with CR2 mediate postbinding events. These are the first studies to be described in which a cell t hat is normally susceptible to viral infection can be manipulated so a s to direct entry of virions via recombinant or endogenous receptors.