Abstract
Epstein-Barr virus (EBV) establishes a persistent latent infection in peripheral B lymphocytes in humans and is associated with a variety of malignancies and proliferative disorders. Latent membrane protein 2A (LMP2A) is one of only two viral proteins expressed in latently infected B lymphocytes in vivo. LMP2A blocks B cell receptor (BCR) signal transduction in vitro by binding the Syk and Lyn protein tyrosine kinases. To analyze the significance of LMP2A expression in vivo, transgenic mice with B cell lineage expression of LMP2A were generated. LMP2A expression results in the bypass of normal B lymphocyte developmental checkpoints allowing immunoglobulin-negative cells to colonize peripheral lymphoid organs, indicating that LMP2A possesses a constitutive signaling activity in nontransformed cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Genetically Modified
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B-Lymphocytes / cytology*
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B-Lymphocytes / virology*
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Bone Marrow Cells / cytology
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Bone Marrow Cells / drug effects
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Bone Marrow Cells / immunology
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Cell Differentiation
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Cell Survival
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Cells, Cultured
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Gene Rearrangement, B-Lymphocyte, Heavy Chain / drug effects
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Gene Rearrangement, B-Lymphocyte, Heavy Chain / physiology
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Genes, RAG-1 / physiology
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Herpesvirus 4, Human / chemistry*
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Herpesvirus 4, Human / immunology*
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Interleukin-7 / pharmacology
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Lymphocyte Activation / drug effects
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Receptors, Antigen, B-Cell / physiology*
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Signal Transduction
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Transgenes / physiology
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Viral Matrix Proteins / genetics
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Viral Matrix Proteins / physiology*
Substances
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EBV-associated membrane antigen, Epstein-Barr virus
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Interleukin-7
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Receptors, Antigen, B-Cell
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Viral Matrix Proteins