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The Epstein-Barr virus-encoded LMP-1 onc ... eron signaling in human B cells
The Epstein-Barr virus-encoded LMP-1 oncoprotein negatively affects Tyk2 phosphorylation and interferon signaling in human B cells.
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Epstein-Barr virus (EBV) establishes a persistent infection in the human host and is associated with a variety of human cancers. Persistent infection results from a balance between the host immune response and viral immune evasion mechanisms. EBV infection is controlled initially by the innate immune response and later by T-cell-mediated adaptive immunity. EBV has evolved mechanisms to evade the host immune response so that it can persist for the lifetime of the host. Latent membrane protein 1 (LMP-1) is the EBV oncoprotein essential for B-cell immortalization by EBV. We show here that LMP-1 interacts with Tyk2, a signaling intermediate in the alpha interferon (IFN-alpha) signaling pathway, via a previously uncharacterized LMP-1 signaling domain. LMP-1 prevents Tyk2 phosphorylation and inhibits IFN-alpha-stimulated STAT2 nuclear translocation and interferon-stimulated response element transcriptional activity. Long-term culture of EBV+ lymphoblastoid cells in IFN-alpha is associated with outgrowth of a population expressing elevated LMP-1 protein levels, suggesting that cells expressing higher levels of LMP-1 survive the antiproliferative selective pressure imposed by IFN-alpha. These results show that LMP-1 can protect EBV+ cells from the IFN-alpha-stimulated antiviral/antiproliferative response and suggest that chronic IFN-alpha treatment may encourage the outgrowth of cells expressing elevated, and therefore potentially oncogenic, LMP-1 levels in EBV+ individuals.
Geiger TR, Martin JM
Journal of virology
2006-12-01 00:00
80
23
11638-50
B-Lymphocytes,Gene Expression Regulation, Viral,Herpesvirus 4, Human,Humans,Interferons,Phosphorylation,Signal Transduction,TYK2 Kinase,Tumor Cells, Cultured,Viral Matrix Proteins,EBV-associated membrane antigen, Epstein-Barr virus,Viral Matrix Proteins,Interferons,TYK2 Kinase
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Campus Box 347, Boulder, CO 80309, USA
J. Virol.
NIAID AI 01537, NCI CA 095043
0022-538X
10.1128/JVI.01570-06
JVI.01570-06
827
True
16987978
