Epstein-Barr virus LMP2A imposes sensitivity to apoptosis.
In cell lines, the Epstein-Barr virus (EBV)-encoded protein latent membrane protein 2A (LMP2A) protects B-cells from apoptosis by blocking B-cell receptor (BCR) signalling. However, EBV-infected B-cells in vivo are extremely different from cell lines. This study used a murine transgenic model in which B-cells express LMP2A and a BCR specific for hen egg lysozyme to determine whether LMP2A protects resting and antigen-activated B-cells from apoptosis. LMP2A allows BCR signal transduction and induces constitutive activation of NF-kappaB to increase Bcl-2 levels that afford LMP2A-mediated protection from apoptosis in the absence or presence of antigen. In contrast, low levels of NF-kappaB inhibitor only affected Bcl-2 and Bcl-xL levels and increased apoptosis in LMP2A-negative B-cells after BCR cross-linking. These data suggest that LMP2A uniquely makes resting B-cells sensitive to NF-kappaB inhibition and apoptosis and suggest that NF-kappaB may be a novel target to eradicate latently EBV-infected B-cells.
Swanson-Mungerson
Michelle
M
Department of Microbiology and Immunology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60516, USA. mswans@midwestern.edu
Bultema
Rebecca
R
Longnecker
Richard
R
D000818:Animals; D000941:Antigens; D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009113:Muramidase / Q000235:genetics / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*
D000941:Antigens; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D011994:Recombinant Proteins; D014763:Viral Matrix Proteins; D009113:Muramidase