Epstein-Barr virus (EBV) latent membrane protein 2A regulates B-cell receptor-induced apoptosis and EBV reactivation through tyrosine phosphorylation.
Epstein-Barr virus (EBV) is a human herpesvirus that establishes a lifelong latent infection of B cells. Within the immune system, apoptosis is a central mechanism in normal lymphocyte homeostasis both during early lymphocyte development and in response to antigenic stimuli. In this study, we found that latent membrane protein 2A (LMP2A) inhibited B-cell receptor (BCR)-induced apoptosis in Burkitt's lymphoma cell lines. Genistein, a specific inhibitor of tyrosine-specific protein kinases, blocked BCR-induced apoptosis and EBV reactivation in the cells. These findings indicate that LMP2A blocks BCR-induced cell apoptosis and EBV reactivation through the inhibition of activation of tyrosine kinases by BCR cross-linking.
Fukuda
Makoto
M
Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave., Chicago, Illinois 60611, USA.
Longnecker
Richard
R
D000956:Antigens, Viral / Q000276:immunology*; D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D004279:DNA, Viral / Q000235:genetics; D019833:Genistein / Q000494:pharmacology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D019000:Phosphotyrosine; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*; D014775:Virus Activation
D000956:Antigens, Viral; D004279:DNA, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D011947:Receptors, Antigen, B-Cell; D014763:Viral Matrix Proteins; D019000:Phosphotyrosine; D019833:Genistein