A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes.
We have isolated a cDNA encoding a novel hematopoietin receptor family member related to the p40 subunit of interleukin-12 and to the ciliary neurotrophic factor receptor, whose expression is induced in B lymphocytes by Epstein-Barr virus (EBV) infection. This gene, which we have designated EBV-induced gene 3 (EBI3), encodes a 34-kDa glycoprotein which lacks a membrane-anchoring motif and is secreted. Despite the absence of a membrane-anchoring motif and of cysteines likely to mediate covalent linkage to an integral membrane protein, EBI3 is also present on the plasma membrane of EBV-transformed B lymphocytes and of transfected cells. Most newly synthesized EBI3 is retained in the endoplasmic reticulum in an endoglycosidase H-sensitive form associated with the molecular chaperone calnexin and with a novel 60-kDa protein. EBI3 is expressed in vivo by scattered cells in interfollicular zones of tonsil tissue, by cells associated with sinusoids in perifollicular areas of spleen tissue, and at very high levels by placental syncytiotrophoblasts. EBI3 expression in vitro is induced in EBV-negative cell lines by expression of the EBV latent infection membrane protein-1 and in peripheral blood mononuclear cells by pokeweed mitogen stimulation. EBI3 maps to chromosome 19p13.2/3, near genes encoding the erythropoietin receptor and the cytokine receptor-associated kinase, Tyk2. EBI3 synthesis by trophoblasts and by EBV-transformed cells and similarities to interleukin-12 p40 are compatible with a role for EBI3 in regulating cell-mediated immune responses.
Devergne
O
O
Department of Microbiology and Molecular Genetics, Harvard University, Boston, Massachusetts, USA.
Hummel
M
M
Koeppen
H
H
Le Beau
M M
MM
Nathanson
E C
EC
Kieff
E
E
Birkenbach
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism* / Q000821:virology; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000378:metabolism; D037281:Calnexin; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers; D018076:DNA, Complementary; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D018664:Interleukin-12 / Q000737:chemistry*; D007378:Interleukins; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D020801:Receptor, Ciliary Neurotrophic Factor; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics*; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry; D014763:Viral Matrix Proteins / Q000378:metabolism; D017735:Virus Latency
D002135:Calcium-Binding Proteins; D017931:DNA Primers; D018076:DNA, Complementary; C097732:EBI3 protein, human; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D006023:Glycoproteins; D007378:Interleukins; D015778:Minor Histocompatibility Antigens; D020801:Receptor, Ciliary Neurotrophic Factor; D018121:Receptors, Cytokine; D017475:Receptors, Nerve Growth Factor; D014763:Viral Matrix Proteins; D037281:Calnexin; D018664:Interleukin-12