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Cancers 2014, 6(3), 1615-1630; https://doi.org/10.3390/cancers6031615

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

Institute for Genetic Medicine, Hokkaido University, N15 W7 Kita-Ku, Sapporo 060-0815, Japan
Received: 20 June 2014 / Revised: 18 July 2014 / Accepted: 21 July 2014 / Published: 6 August 2014
(This article belongs to the Special Issue DNA Viruses in Human Cancer)
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Abstract

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. View Full-Text
Keywords: Epstein-Barr virus; EBER; oncogenesis; innate immunity Epstein-Barr virus; EBER; oncogenesis; innate immunity
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Iwakiri, D. Epstein-Barr Virus-Encoded RNAs: Key Molecules in Viral Pathogenesis. Cancers 2014, 6, 1615-1630.

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