Epstein-Barr virus coopts lipid rafts to block the signaling and antigen transport functions of the BCR.
The B cell antigen receptor (BCR) functions to initiate signaling and to internalize antigen for processing from within Lyn kinase-enriched membrane lipid rafts. The signaling function of the BCR is blocked by Epstein-Barr Virus (EBV) latent membrane protein 2A (LMP2A), which is constitutively phosphorylated by Lyn. Here, we show that LMP2A resides in lipid rafts and excludes the BCR from entering rafts by Lyndependent mechanisms, thus blocking both BCR signaling and antigen transport. Mutant LMP2A that permits BCR signaling and raft translocation still blocks antigen trafficking, indicating independent control of these BCR functions. Thus, EBV coopts the lipid rafts to disarm both the signaling and antigen-processing functions of the BCR by independent mechanisms.
Dykstra
M L
ML
Laboratory of Immunogenetics, National Institute of Allergy, and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Longnecker
R
R
Pierce
S K
SK
D017951:Antigen Presentation / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology* / Q000378:metabolism; D001692:Biological Transport; D003432:Cross-Linking Reagents; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D021962:Membrane Microdomains / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000276:immunology* / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
D000956:Antigens, Viral; D003432:Cross-Linking Reagents; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D011947:Receptors, Antigen, B-Cell; D014763:Viral Matrix Proteins; D019061:src-Family Kinases