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 camouflaged with glycoprotein 350/220, which mimics the human ligand C3dg and thereby binds to and exploits complement receptor type 2 (CR2; CD21), the EBV receptor. It has not been possible to determine the role of CR2 during postbinding events of viral infection because all B lymphocytes express endogenous CR2, precluding an informative study of receptor 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 first, that two discontinuous amino acid substitutions within the ligand-binding domain of murine CR2 render it capable of mediating EBV infection of human B-lymphoblastoid cells, and second, that the specific role of CR2 during EBV infection is to capture virions at the cell surface, after which cofactors not associated with CR2 mediate postbinding events. These are the first studies to be described in which a cell that is normally susceptible to viral infection can be manipulated so as to direct entry of virions via recombinant or endogenous receptors.
Martin
D R
DR
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Marlowe
R L
RL
Ahearn
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000382:microbiology*; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011951:Receptors, Complement / Q000378:metabolism; D017464:Receptors, Complement 3d / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology*; D014779:Virus Replication
D015815:Cell Adhesion Molecules; D009838:Oligodeoxyribonucleotides; D011951:Receptors, Complement; D017464:Receptors, Complement 3d; D011991:Receptors, Virus; D018799:Intercellular Adhesion Molecule-1