Functional delivery of viral miRNAs via exosomes

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