1. Epstein–Barr virus Latent Membrane Protein 2A (LMP2A)-mediated changes in Fas expression and Fas-dependent apoptosis: Role of Lyn/Syk activation
- Author
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Kathryn T. Bieging, Amanda L Stone, Michael J. Fay, Samira Hussain, Ryan Incrocci, Michelle Swanson-Mungerson, and Lauren A.C. Alt
- Subjects
Herpesvirus 4, Human ,viruses ,Immunology ,B-cell receptor ,Receptors, Antigen, B-Cell ,Syk ,Apoptosis ,Biology ,medicine.disease_cause ,Article ,Cell Line ,Viral Matrix Proteins ,Mice ,LYN ,hemic and lymphatic diseases ,otorhinolaryngologic diseases ,medicine ,Animals ,Humans ,Syk Kinase ,fas Receptor ,B cell ,B-Lymphocytes ,Intracellular Signaling Peptides and Proteins ,Germinal center ,Protein-Tyrosine Kinases ,Fas receptor ,Epstein–Barr virus ,Cell biology ,Enzyme Activation ,stomatognathic diseases ,src-Family Kinases ,medicine.anatomical_structure ,Mutation ,Cancer research - Abstract
Epstein-Barr virus Latent Membrane Protein 2A (LMP2A) is expressed in EBV-infected B cells in the germinal center, a site of significant apoptosis induced by engagement of Fas on activated B cells. Signals from the B cell receptor (BCR) protect germinal center B cells from Fas-mediated apoptosis, and since LMP2A is a BCR mimic, we hypothesized that LMP2A would also protect B cells from Fas-mediated apoptosis. Surprisingly, latently-infected human and murine B cell lines expressing LMP2A were more sensitive to Fas-mediated apoptosis, as determined by increases in Annexin-V staining, and cleavage of caspase-8, −3 and PARP. Additional studies show that LMP2A-expressing B cell lines demonstrate a Lyn- and Syk-dependent increase in sensitivity to Fas-mediated apoptosis, due to an LMP2A-dependent enhancement in Fas expression. These findings demonstrate the ability for LMP2A to directly increase a pro-apoptotic molecule and have implications for EBV latency as well as the treatment of EBV-associated malignancies.
- Published
- 2015
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