Epstein-Barr Virus Small RNA (EBER) Genes: Differential Regulation during Lytic Viral Replication

Greifenegger, Norbert; Jäger, Michael; Kunz‐Schughart, Leoni A.; Wolf, Hans; Schwarzmann, Fritz

doi:10.1128/jvi.72.11.9323-9328.1998

Cited by 36 publications

(15 citation statements)

References 25 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…EBER expression appears to be affected by the state of viral life cycle status. A previous study demonstrated downregulated EBER transcription during the switch from latent infection to lytic viral replication [ 25 ]. In contrast, the amounts of EBERs remain unaltered within 72 h after the induction of lytic replication.…”

Section: Synthesis and Expression Of Ebersmentioning

confidence: 99%

Epstein-Barr Virus-Encoded RNAs: Key Molecules in Viral Pathogenesis

Iwakiri

2014

Cancers

View full text Add to dashboard Cite

The Epstein-Barr virus (EBV) is known as an oncogenic herpesvirus that has been implicated in the pathogenesis of various malignancies. EBV-encoded RNAs (EBERs) are non-coding RNAs expressed abundantly in latently EBV-infected cells. Herein, I summarize the current understanding of the functions of EBERs, including the interactions with cellular factors through which EBERs contribute to EBV-mediated pathogenesis. Previous studies have demonstrated that EBERs are responsible for malignant phenotypes in lymphoid cells, and can induce several cytokines that can promote the growth of various EBV-infected cancer cells. EBERs were also found to bind retinoic acid-inducible gene I (RIG-I) and thus activate its downstream signaling. Furthermore, EBERs induce interleukin-10, an autocrine growth factor for Burkitt’s lymphoma cells, by activating RIG-I/interferon regulatory factor 3 pathway, suggesting that EBER-mediated innate immune signaling modulation contributes to EBV-mediated oncogenesis. Recently, EBV-infected cells were reported to secret EBERs, which were then recognized by toll-like receptor 3 (TLR3), leading to the induction of type I interferon and inflammatory cytokines, and subsequent immune activation. Furthermore, EBER1 was detected in the sera of patients with active EBV-infectious diseases, suggesting that EBER1-meidated TLR3 signaling activation could account for the pathogenesis of active EBV-infectious diseases.

show abstract

Section: Synthesis and Expression Of Ebersmentioning

confidence: 99%

Epstein-Barr Virus-Encoded RNAs: Key Molecules in Viral Pathogenesis

Iwakiri

2014

Cancers

View full text Add to dashboard Cite

show abstract

“…However, during the transition from latent infection to lytic replication of EBV, transcription of EBERs remains unaltered for 72 h, and, thereafter, transcription of EBER1 is remarkably down‐regulated, whereas the transcription of EBER2 is affected only to a minor extent. ( 25 )…”

Section: Transcriptional Regulation Of Eber1 and Eber2 Genesmentioning

confidence: 99%

Modulation of innate immunity system by Epstein–Barr virus‐encoded non‐coding RNA and oncogenesis

Samanta

Takada²

2009

Cancer Science

View full text Add to dashboard Cite

Epstein–Barr virus (EBV)‐encoded small RNAs (EBERs) are polyA–, non‐coding RNAs that are expressed abundantly in all forms of cells latently infected with EBV. EBERs (EBER1 and EBER2) contribute to the clonal proliferation of EBV‐negative Burkitt’s lymphoma (BL) cells in soft agar, tumorigenicity in SCID mice, up‐regulation of the bcl‐2 oncoprotein, resistance to apoptosis, and maintenance of malignant phenotypes in BL cells. EBERs induce the expression of interleukin (IL)‐10 in BL cells, insulin‐like growth factor 1 (IGF‐I) in gastric and nasopharyngeal carcinoma cells, IL‐9 in T cells, and IL‐6 in lymphoblastoid cell lines. Additionally, each of these cytokines acts as an autocrine growth factor. In BL cells, EBERs bind the double‐stranded RNA‐activated protein kinase PKR, inhibit its phosphorylation, and thereby prevent IFN‐α‐mediated apoptosis. In epithelial cells, EBERs confer resistance to Fas‐mediated apoptosis by blocking PKR activity. EBERs form complexes with PKR, ribosomal protein L22, lupus erythematosis‐associated antigen (La), and retinoic acid‐inducible gene I (RIG‐I). In BL cells, EBERs activate RIG‐I signaling and induce the expression of type‐I IFNs and interferon stimulated genes (ISGs) through the activation of RIG‐I substrates, nuclear factor‐kappa B (NF‐κB), and IFN regulatory factor 3 (IRF‐3), and anti‐inflamatory cytokine IL‐10 through IRF‐3 but not NF‐κB signaling. EBERs also play critical roles in the growth transformation of B lymphocytes. Although EBER1 and EBER2 exhibit similarities in their primary (54%) and secondary structures, recent findings have shown that recombinant EBVs carrying only the EBER2 gene play a greater role in the growth transformation of B lymphocytes than EBVs carrying only the EBER1 gene. Thus, EBERs play multiple roles in various cell types, and we present a model that highlights the functions of EBERs in EBV‐mediated oncogenesis in BL cells. (Cancer Sci 2009)

show abstract

“…The PapilloCheck (Greiner BioOneGmbH, Frickenhausen, Germany) is a PCR method that identifies 13 high-risk HPV types (HPV 16,18,31,33,35,39,45,51,52,56,58,59, and 68), five possibly oncogenic HPV types (HPV 53, 66, 70, 73, and 82), and six low-risk HPV types (HPV 6, 11, 40, 42, 43, and 44). PapilloCheck uses multiplex PCR with fluorescent primers to amplify DNA fragments (350 nucleotides) within the E1 open reading frame of the HPV genome.…”

Section: Hpv Detection and Pcrmentioning

confidence: 99%

Mapping of human papilloma virus, p16, and epstein‐barr virus in non‐malignant tonsillar disease

Holm

Schindele

Allard

et al. 2019

Laryngoscope Investig Oto

View full text Add to dashboard Cite

Objectives Due to their location in the entrance of the aero‐digestive tract, tonsils are steadily exposed to viruses. Human papilloma virus (HPV) and Epstein‐Barr virus (EBV) are two potentially oncogenic viruses that tonsils encounter. The incidence of HPV positive tonsillar cancer is on the rise and it is unknown when infection with HPV occurs. Aim To investigate if tonsils are infected with HPV and EBV, to study the co‐expression of HPV and its surrogate marker p16, and to evaluate the number of EBV positive cells in benign tonsillar disease. Materials and Methods Tonsils from 40 patients in a university hospital were removed due to hypertrophy, chronic or recurrent infection. These were analyzed for presence of HPV, its surrogate marker p16, and EBV. HPV was studied using PapilloCheck (a PCR method), while p16 was identified in epithelial and lymphoid tissue with immunohistochemistry and EBV using EBER‐ISH (Epstein‐Barr encoding region–in situ hybridization). Results HPV was not detected, and p16 was present at low numbers in all epithelial samples as well as in 92.5% of the lymphoid tonsillar samples. At least one EBER‐positive cell was seen in 65% of cases. Larger numbers of EBER‐expressing cells were only seen in two cases. Conclusion These findings demonstrate that EBV and HPV infect tonsils independently, but further studies are warranted to confirm their infectious relationship. Level of Evidence Cross‐sectional study

show abstract

Epstein-Barr Virus Small RNA (EBER) Genes: Differential Regulation during Lytic Viral Replication

Cited by 36 publications

References 25 publications

Epstein-Barr Virus-Encoded RNAs: Key Molecules in Viral Pathogenesis

Epstein-Barr Virus-Encoded RNAs: Key Molecules in Viral Pathogenesis

Modulation of innate immunity system by Epstein–Barr virus‐encoded non‐coding RNA and oncogenesis

Mapping of human papilloma virus, p16, and epstein‐barr virus in non‐malignant tonsillar disease

Contact Info

Product

Resources

About