A novel function for the Epstein-Barr virus transcription factor EB1/Zta: induction of transcription of the hIL-10 gene.
Interleukin-10 (IL-10) plays a critical role in Epstein-Barr virus (EBV) biology. Indeed, the EBV genome contains a gene (BCRF1) with homology to the human IL-10 (hIL-10) gene. In addition to viral IL-10, which is secreted late in the productive cycle, hIL-10 production is also induced in B cells infected by EBV. The EBV protein LMP-1 and the viral small non-polyadenylated RNAs (EBERs) expressed during latency are involved in hIL-10 induction. In this study, we show that in B cells the viral transcription factor EB1, which is the main inducer of the EBV productive cycle, also activates transcription of the hIL-10 gene and secretion of the hIL-10 protein. Accordingly, EB1 bound directly to specific DNA sequences in the hIL-10 minimal promoter. Moreover, specific disruption of EB1 binding to some of these sites impaired EB1-mediated activation of transcription at the hIL-10 promoter in a transient expression assay. Therefore, an increase in IL-10 production occurs during latency and early and late during the productive cycle. This production of IL-10 might favour the survival of EBV-infected cells in vivo and/or create a microenvironment required for efficient de novo infection of B lymphocytes by EBV virions.
Mahot
Segolene
S
Laboratoire de Virologie Moléculaire et Structurale, UPRES-EA2939, GDR CNRS 2372, Université Joseph-Fourier Grenoble I, 38706 La Tronche, France.
Sergeant
Alain
A
U412 INSERM, ENS-Lyon, 46 allée d'Italie, 69364 Lyon Cedex 07, France.
Drouet
Emmanuel
E
Laboratoire de Virologie Moléculaire et Structurale, UPRES-EA2939, GDR CNRS 2372, Université Joseph-Fourier Grenoble I, 38706 La Tronche, France.
Gruffat
Henri
H
U412 INSERM, ENS-Lyon, 46 allée d'Italie, 69364 Lyon Cedex 07, France.
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000502:physiology*
C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D015534:Trans-Activators; D014764:Viral Proteins; D016753:Interleukin-10