Epstein-Barr virus (EBV)-encoded small RNA is released from EBV-infected cells and activates signaling from Toll-like receptor 3.

Abstract

Epstein-Barr virus-encoded small RNA (EBER) is nonpolyadenylated, noncoding RNA that forms stem-loop structure by intermolecular base-pairing, giving rise to double-stranded RNA (dsRNA)-like molecules, and exists abundantly in EBV-infected cells. Here, we report that EBER induces signaling from the Toll-like receptor 3 (TLR3), which is a sensor of viral double-stranded RNA (dsRNA) and induces type I IFN and proinflammatory cytokines. A substantial amount of EBER, which was sufficient to induce signaling from TLR3, was released from EBV-infected cells, and the majority of the released EBER existed as a complex with a cellular EBER-binding protein La, suggesting that EBER was released from the cells by active secretion of La. Sera from patients with infectious mononucleosis (IM), chronic active EBV infection (CAEBV), and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), whose general symptoms are caused by proinflammatory cytokines contained EBER, and addition of RNA purified from the sera into culture medium induced signaling from TLR3 in EBV-transformed lymphocytes and peripheral mononuclear cells. Furthermore, DCs treated with EBER showed mature phenotype and antigen presentation capacity. These findings suggest that EBER, which is released from EBV-infected cells, is responsible for immune activation by EBV, inducing type I IFN and proinflammatory cytokines. EBER-induced activation of innate immunity would account for immunopathologic diseases caused by active EBV infection.

• Authors: Dai Iwakiri, Li Zhou, Mrinal Samanta, Misako Matsumoto, Takashi Ebihara, Tsukasa Seya, Shosuke Imai, Mikiya Fujieda, Keisei Kawa, Kenzo Takada
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 206 Issue 10 Pg. 2091-9 (Sep 28 2009) ISSN: 1540-9538 [Electronic] United States
• PMID: 19720839 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Epstein-Barr virus encoded RNA 1
• Epstein-Barr virus encoded RNA 2
• RNA, Viral
• TLR3 protein, human
• Toll-Like Receptor 3
• Interferon-beta

Topics

• Cell Line, Tumor
• Cytokines (biosynthesis)
• Dendritic Cells (physiology)
• Humans
• Interferon-beta (biosynthesis)
• RNA, Viral (analysis, physiology)
• Signal Transduction (physiology)
• Toll-Like Receptor 3 (physiology)