Human complement receptor type 1/CD35 is an Epstein-Barr Virus receptor

Cell Rep. 2013 Feb 21;3(2):371-85. doi: 10.1016/j.celrep.2013.01.023. Epub 2013 Feb 14.


Epstein-Barr virus (EBV) attachment to primary B cells initiates virus entry. Although CD21 is the only known receptor for EBVgp350/220, a recent report documents EBV-infected B cells from a patient genetically deficient in CD21. On normal resting B cells, CD21 forms two membrane complexes: one with CD19 and another with CD35. Whereas the CD21/CD19 complex is widely retained on immortalized and B cell tumor lines, the related complement-regulatory protein CD35 is lost. To determine the role(s) of CD35 in initial infection, we transduced a CD21-negative pre-B cell and myeloid leukemia line with CD35, CD21, or both. Cells expressing CD35 alone bound gp350/220 and became latently infected when the fusion receptor HLA II was coexpressed. Temporal, biophysical, and structural characteristics of CD35-mediated infection were distinct from CD21. Identification of CD35 as an EBV receptor uncovers a salient role in primary infection, addresses unsettled questions of virus tropism, and underscores the importance of EBVgp350/220 for vaccine development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD19 / metabolism
  • Cell Line
  • Herpesvirus 4, Human / metabolism*
  • Humans
  • K562 Cells
  • Mutation
  • Precursor Cells, B-Lymphoid / immunology
  • Precursor Cells, B-Lymphoid / metabolism
  • Protein Binding
  • Receptors, Complement 3b / genetics
  • Receptors, Complement 3b / metabolism*
  • Receptors, Complement 3d / genetics
  • Receptors, Complement 3d / metabolism*
  • Temperature
  • Transfection
  • Viral Matrix Proteins / metabolism
  • Virus Attachment
  • Virus Internalization


  • Antigens, CD19
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Receptors, Complement 3b
  • Receptors, Complement 3d
  • Viral Matrix Proteins