Epstein-Barr virus latent membrane protein 2A mimics B-cell receptor-dependent virus reactivation.
Latent membrane protein 2A (LMP2A) of Epstein-Barr virus (EBV) shares protein motifs with the B-cell receptor that play a role in B-cell receptor signalling and has been shown to mimic an activated B-cell receptor by providing a survival signal for mature B cells in transgenic mice. Conversely, LMP2A has been reported not to support but to inhibit B-cell receptor signalling with respect to virus reactivation and to block lytic virus induction after anti-Ig treatment of EBV-infected B cells. To solve this apparent paradox, the role of LMP2A in lytic-cycle induction was re-examined in B cells conditionally immortalized by EBV. It was shown that, in the absence of other stimuli, LMP2A expression alone could lead to induction of the virus lytic cycle. Similarly to B-cell receptor stimulation by anti-Ig treatment, this LMP2A-mediated reactivation was dependent on the mitogen-activated protein kinase pathway and could be inhibited by the viral LMP1. Our data reinforce the notion that LMP2A is a functional homologue of the B-cell receptor, not only with respect to B-cell survival but also with respect to regulation of the lytic cycle.
Schaadt
Eveline
E
GSF-Research Center for Environment and Health, Institute for Clinical Molecular Biology and Tumor Genetics, Marchioninistrasse 25, D-81377 Munich, Germany.
Baier
Barbara
B
GSF-Research Center for Environment and Health, Institute for Clinical Molecular Biology and Tumor Genetics, Marchioninistrasse 25, D-81377 Munich, Germany.
Mautner
Josef
J
GSF-Research Center for Environment and Health, Institute for Clinical Molecular Biology and Tumor Genetics, Marchioninistrasse 25, D-81377 Munich, Germany.
Bornkamm
Georg W
GW
GSF-Research Center for Environment and Health, Institute for Clinical Molecular Biology and Tumor Genetics, Marchioninistrasse 25, D-81377 Munich, Germany.
Adler
Barbara
B
GSF-Research Center for Environment and Health, Institute for Clinical Molecular Biology and Tumor Genetics, Marchioninistrasse 25, D-81377 Munich, Germany.
D001402:B-Lymphocytes / Q000502:physiology / Q000821:virology*; D002478:Cells, Cultured; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D018716:Molecular Mimicry / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism* / Q000502:physiology; D014763:Viral Matrix Proteins / Q000502:physiology*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D011947:Receptors, Antigen, B-Cell; D014763:Viral Matrix Proteins