An integral membrane protein (LMP2) blocks reactivation of Epstein-Barr virus from latency following surface immunoglobulin crosslinking

Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):772-6. doi: 10.1073/pnas.91.2.772.


The role of latent membrane protein 2 (LMP2) in Epstein-Barr virus (EBV) infection was evaluated by using latently infected primary B lymphocytes that had been growth transformed by wild-type or specifically mutated EBV recombinants. LMP2 null mutant recombinant EBV-infected cells were similar to normal B lymphocytes in their rapid increase in intracellular free calcium after surface immunoglobulin crosslinking. These cells also became more permissive for lytic EBV replication. In sharp contrast, wild-type control infected cells had little or no increase in intracellular free calcium or in permissivity for EBV replication. The block to surface immunoglobulin crosslinking-induced permissivity in cells expressing wild-type LMP2 could be bypassed by raising intracellular free calcium levels with an ionophore and by activating protein kinase C with phorbol 12-myristate 13-acetate. LMP2A, not LMP2B, mediates this effect on calcium mobilization. Genetic and biochemical data are consistent with these effects being due to the interaction of the LMP2A N-terminal cytoplasmic domain with B lymphocyte src family tyrosine kinases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology*
  • Calcimycin / pharmacology
  • Calcium / metabolism
  • Capsid / immunology
  • Cell Line, Transformed
  • Cell Transformation, Viral
  • Cross-Linking Reagents
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / immunology*
  • Herpesvirus 4, Human / physiology
  • Humans
  • Molecular Sequence Data
  • Protein Kinase C / metabolism
  • Receptors, Antigen, B-Cell / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology*
  • Virus Activation / immunology
  • Virus Replication / drug effects


  • Antigens, Viral
  • Cross-Linking Reagents
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Receptors, Antigen, B-Cell
  • Viral Matrix Proteins
  • Calcimycin
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate
  • Calcium