Epstein–Barr virus growth/latency III program alters cellular microRNA expression

Cameron, Jennifer E.; Fewell, Claire; Yin, Qinyan; McBride, Jane; Wang, Xia; Lin, Zhen; Flemington, Erik K.

doi:10.1016/j.virol.2008.09.018

Cited by 134 publications

(131 citation statements)

References 44 publications

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“…29 In contrast, in our study we identified differentially expressed, host-encoded miRNAs in EBV-infected versus noninfected cells. Thereby, we observed elevated expression levels of mir-221 and mir-222, which have not previously been reported reported by our group upon EBV infection.…”

Section: Resultscontrasting

confidence: 59%

NcRNA-microchip analysis

Hutzinger

Mrázek²,

Vorwerk³

et al. 2010

RNA Biology

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Section: Resultscontrasting

confidence: 59%

NcRNA-microchip analysis

Hutzinger

Mrázek²,

Vorwerk³

et al. 2010

RNA Biology

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“…S3A). Surprisingly, in the X50-7 LCL that also expresses all BART miRNAs (20), cluster 2 BART miRNAs were ∼1,000-fold less abundant in exosomes (Fig. 1G).…”

Section: Resultsmentioning

confidence: 96%

Functional delivery of viral miRNAs via exosomes

Pegtel

Cosmopoulos

Thorley‐Lawson

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

1,455

1,227

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Noncoding regulatory microRNAs (miRNAs) of cellular and viral origin control gene expression by repressing the translation of mRNAs into protein. Interestingly, miRNAs are secreted actively through small vesicles called "exosomes" that protect them from degradation by RNases, suggesting that these miRNAs may function outside the cell in which they were produced. Here we demonstrate that miRNAs secreted by EBV-infected cells are transferred to and act in uninfected recipient cells. Using a quantitative RT-PCR approach, we demonstrate that mature EBV-encoded miRNAs are secreted by EBV-infected B cells through exosomes. These EBV-miRNAs are functional because internalization of exosomes by MoDC results in a dose-dependent, miRNAmediated repression of confirmed EBV target genes, including CXCL11/ ITAC, an immunoregulatory gene down-regulated in primary EBVassociated lymphomas. We demonstrate that throughout coculture of EBV-infected B cells EBV-miRNAs accumulate in noninfected neighboring MoDC and show that this accumulation is mediated by transfer of exosomes. Thus, the exogenous EBV-miRNAs transferred through exosomes are delivered to subcellular sites of gene repression in recipient cells. Finally, we show in peripheral blood mononuclear cells from patients with increased EBV load that, although EBV DNA is restricted to the circulating B-cell population, EBV BART miRNAs are present in both B-cell and non-B-cell fractions, suggestive of miRNA transfer. Taken together our findings are consistent with miRNA-mediated gene silencing as a potential mechanism of intercellular communication between cells of the immune system that may be exploited by the persistent human γ-herpesvirus EBV.

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“…Similarly to miRNA-146a, miRNA-155 has also been implicated in a variety of pathologies 8,9,10 . However, in the case of SS and in relation to the viral differentially expressed microRNA reported in this article, the relation of miRNA-155 to Epstein-Barr virus infection (EBV) 11,12 and the association of this microRNA to lymphomas deserve further evaluation 13,14,15 .…”

Section: Human and Viral Microrna Expression In Sjögren Syndromementioning

confidence: 92%