Epstein-Barr virus-induced genes: first lymphocyte-specific G protein-coupled peptide receptors

Abstract

Since Epstein-Barr virus (EBV) infection of Burkitt's lymphoma (BL) cells in vitro reproduces many of the activation effects of EBV infection of primary B lymphocytes, mRNAs induced in BL cells have been cloned and identified by subtractive hybridization. Nine genes encode RNAs which are 4-to >100-fold more abundant after EBV infection. Two of these, the genes for CD21 and vimentin, were previously known to be induced by EBV infection. Five others, the genes for cathepsin H, annexin VI (p68), serglycin proteoglycan core protein, CD44, and the myristylated alanine-rich protein kinase C substrate (MARCKS), are genes which were not previously known to be induced by EBV infection. Two novel genes, EBV-induced genes 1 and 2 (EBI 1 and EBI 2, respectively) can be predicted from their cDNA sequences to encode G protein-coupled peptide receptors. EBI 1 is expressed exclusively in Band T-lymphocyte cell lines and in lymphoid tissues and is highly homologous to the interleukin 8 receptors. EBI 2 is most closely related to the thrombin receptor. EBI 2 is expressed in B-lymphocyte cell lines and in lymphoid tissues but not in T-lymphocyte cell lines or peripheral blood T lymphocytes. EBI 2 is also expressed at lower levels in a promyelocytic and a histiocytic cell line and in pulmonary tissue. These predicted G protein-coupled peptide receptors are more likely to be mediators of EBV effects on B lymphocytes or of normal lymphocyte functions than are genes previously known to be This research was supported by grant CA47006 from the National

In vivo control of B‐cell survival and antigen‐specific B‐cell responses

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EBI2 regulates intracellular signaling and migration in human astrocyte

“…T he G protein-coupled receptor (GPCR), EBI2 (Epstein-Barr virus (EBV)-induced gene 2, aka GPR183) is highly expressed in immune cells and activated by oxysterols (Birkenbach et al, 1993;Hannedouche et al, 2011;Liu et al, 2011). EBI2 signals through the pertussis toxin (PTx)-sensitive heterotrimeric G proteins of the Gi/o family leading to a decrease in cAMP production, calcium mobilization, and stimulation of the extracellular-signal-regulated kinase (ERK) pathway (Benned-Jensen et al, 2013;Gatto et al, 2011).…”

EBI2 regulates CXCL13‐mediated responses by heterodimerization with CXCR5

“…Recent studies in B cells identified the gene for the Epstein-Barr virus-induced molecule 2 (EBI2), a member of the G-protein-coupled receptor (GPCR) family (8). EBI2 mRNA is detected constitutively in naive B cells, and its level increases after activation (6,9,10).…”