Transcriptional analysis of the Epstein--Barr virus interleukin-10 homologue during the lytic cycle

Robert, Thomas; Cochet, C; Joab, Irène

doi:10.1099/0022-1317-77-6-1163

Cited by 18 publications

(17 citation statements)

References 11 publications

(23 reference statements)

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“…Previous screening of this library revealed its potential to delineate important molecular events occurring early in the pathway toward cellular transformation, at a time when EBV latency genes are initially activated within the B cell (40). Indeed, the EBV homolog of human IL-10, viral IL-10, was isolated from this library, initiating studies that confirmed it as a critical element, not only during viral replication (46), but in the establishment of latency and growth transformation in primary B cells (8,47).…”

Section: Discussionmentioning

confidence: 91%

Sustained Expression of the Novel EBV-Induced Zinc Finger Gene, ZNF EB, Is Critical for the Transition of B Lymphocyte Activation to Oncogenic Growth Transformation

Tune

Pilon

Saiki

et al. 2002

The Journal of Immunology

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EBV is a human tumor virus that infects and establishes latency in the majority of humans worldwide. In vitro, EBV growth transforms primary B lymphocytes into lymphoblastoid cell lines with high efficiency. We have used cDNA subtraction cloning to identify cellular target genes required for growth transformation and identified a new C2H2 (Krüppel-type) zinc finger gene, ZNFEB, that is trans-activated early following EBV infection. In this study, we characterize ZNFEB, including its intronless locus, and human and mouse protein variants. The gene is transiently expressed during normal lymphocyte activation, and its expression is sustained in EBV-positive but not EBV-negative B cell lines. There is limited expression in nonhemopoietic tissues. Its critical role in the growth transformation of B lineage cells is indicated by the abrogation of transformation with antisense strategies. ZNFEB maps to chromosome 18q12, a region with mutations in numerous, predominantly hemopoietic malignancies.

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Section: Discussionmentioning

confidence: 91%

Sustained Expression of the Novel EBV-Induced Zinc Finger Gene, ZNF EB, Is Critical for the Transition of B Lymphocyte Activation to Oncogenic Growth Transformation

Tune

Pilon

Saiki

et al. 2002

The Journal of Immunology

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“…Although not expressed as abundantly as the leftward oriP transcripts, the previously described upstream initiated BCRF1 transcripts (22)(23)(24) are similarly likely to perform functions in the reactivation cascade, and we propose that these roles are distinct from making BCRF1 protein. Since long 5= UTRs tend to be inefficient substrates for translation, it is more likely that the 5= extended BCRF1 transcripts have noncoding functions.…”

Section: Pervasiveness and Functional Significance Of Lytic Vlncrnasmentioning

confidence: 90%

“…Previous studies showed that the BCRF1/vIL10 open reading frame is transcribed not only from a proximal promoter but also from multiple upstream promoters located within and 5= to oriP (Fig. 1A) (22)(23)(24). Analysis of strand-specific RNA-seq data from induced Akata cells showed strong rightward transcription across the BCRF1 reading frame, much of which likely originates from the proximal BCRF1 promoter (Fig.…”

Section: Lytic Transcription At the Ebv Latency Origin Of Replicationmentioning

confidence: 99%

New Noncoding Lytic Transcripts Derived from the Epstein-Barr Virus Latency Origin of Replication, oriP , Are Hyperedited, Bind the Paraspeckle Protein, NONO/p54nrb, and Support Viral Lytic Transcription

Cao

Moss

O’Grady

et al. 2015

J Virol

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We have previously shown that the Epstein-Barr virus (EBV) likely encodes hundreds of viral long noncoding RNAs (vlncRNAs) that are expressed during reactivation. Here we show that the EBV latency origin of replication (oriP) is transcribed bi-directionally during reactivation and that both leftward (oriPtLs) and rightward (oriPtRs) transcripts are largely localized in the nucleus. While the oriPtLs are most likely noncoding, at least some of the oriPtRs contain the BCRF1/vIL10 open reading frame. Nonetheless, oriPtR transcripts with long 5= untranslated regions may partially serve noncoding functions. Both oriPtL and oriPtR transcripts are expressed with late kinetics, and their expression is inhibited by phosphonoacetic acid. RNA sequencing (RNA-seq) analysis showed that oriPtLs and oriPtRs exhibited extensive "hyperediting" at their Family of Repeat (FR) regions. RNA secondary structure prediction revealed that the FR region of both oriPtLs and oriPtRs may form large evolutionarily conserved and thermodynamically stable hairpins. The doublestranded RNA-binding protein and RNA-editing enzyme ADAR was found to bind to oriPtLs, likely facilitating editing of the FR hairpin. Further, the multifunctional paraspeckle protein, NONO, was found to bind to oriPt transcripts, suggesting that oriPts interact with the paraspeckle-based innate antiviral immune pathway. Knockdown and ectopic expression of oriPtLs showed that it contributes to global viral lytic gene expression and viral DNA replication. Together, these results show that these new vlncRNAs interact with cellular innate immune pathways and that they help facilitate progression of the viral lytic cascade. IMPORTANCERecent studies have revealed that the complexity of lytic herpesviral transcriptomes is significantly greater than previously appreciated with hundreds of viral long noncoding RNAs (vlncRNAs) being recently discovered. Work on cellular lncRNAs over the past several years has just begun to give us an initial appreciation for the array of functions they play in complex formation and regulatory processes in the cell. The newly identified herpesvirus lncRNAs are similarly likely to play a variety of different functions, although these functions are likely tailored to specific needs of the viral infection cycles. Here we describe novel transcripts derived from the EBV latency origin of replication. We show that they are hyperedited, that they interact with a relatively newly appreciated antiviral pathway, and that they play a role in facilitating viral lytic gene expression. These investigations are a starting point to unraveling the complex arena of vlncRNA function in herpesvirus lytic replication. The Epstein-Barr virus (EBV) is an oncogenic human herpesvirus that infects 95% of the world's population (1). Although infection is typically asymptomatic, the virus will persist in the host for the duration of its life. In most immunocompetent individuals, the virus poses little serious health risk and its presence is unremarkable. Nevertheless, in...

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“…BamHI-C fragment rightward reading frame 1 (BCRF1) is a late gene during the lytic phase that encodes viral interleukin-10 (vIL-10), a human homolog of interleukin-10 (hIL-10) [7,8]. vIL-10 is not only expressed in the early phase but also the late phase of virus replication when EBV infects human B cells [9][10][11]. The vIL-10 protein performs functions similar to those of hIL-10 protein, which is mostly involved in immunosuppression [12].…”

Section: Epstein-barr Virus (Ebv) Is a Known Carcinogenic Agentmentioning

confidence: 99%

Sequence variation of Epstein-Barr virus (EBV) BCRF1 in lymphomas in non-endemic areas of nasopharyngeal carcinoma

et al. 2014

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To characterize the sequence variation and the potential implication of the Epstein-Barr virus (EBV) oncogene in lymphoma, BamHI-C fragment rightward reading frame 1 (BCRF1) was sequenced in different types of EBV-positive lymphoma in northern China, and polymorphisms were compared with previous variation data from other malignancies. The dominate subtype of BCRF1 in EBV-positive lymphoma was the B95-8 prototype, and a mutation in the signal peptide was more strongly associated with Hodgkin's lymphoma. The high conservation of BCRF1 in EBV-positive lymphoma suggests its important role in maintaining the basic biological activity and immunosuppressive functions of the virus.

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Transcriptional analysis of the Epstein--Barr virus interleukin-10 homologue during the lytic cycle

Cited by 18 publications

References 11 publications

Sustained Expression of the Novel EBV-Induced Zinc Finger Gene, ZNF EB, Is Critical for the Transition of B Lymphocyte Activation to Oncogenic Growth Transformation

Sustained Expression of the Novel EBV-Induced Zinc Finger Gene, ZNF EB, Is Critical for the Transition of B Lymphocyte Activation to Oncogenic Growth Transformation

New Noncoding Lytic Transcripts Derived from the Epstein-Barr Virus Latency Origin of Replication, oriP , Are Hyperedited, Bind the Paraspeckle Protein, NONO/p54nrb, and Support Viral Lytic Transcription

Sequence variation of Epstein-Barr virus (EBV) BCRF1 in lymphomas in non-endemic areas of nasopharyngeal carcinoma

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