Abstract
BackgroundEpstein-Barr virus (EBV) is an etiological cause of many human lymphocytic and epithelial malignancies. EBV expresses different genes that are associated with three latency types. To date, as many as 44 EBV-encoded miRNA species have been found, but their comprehensive profiles in the three types of latent infection that are associated with various types of tumors are not well documented.MethodsIn the present study, we utilized poly (A)-tailed quantitative real-time RT-PCR in combination with microarray analysis to measure the relative abundances of viral miRNA species in a subset of representative lymphoid and epithelial tumor cells with various EBV latency types.ResultsOur findings showed that the miR-BHRF1 and miR-BART families were expressed differentially in a tissue- and latency type-dependent manner. Specifically, in nasopharyngeal carcinoma (NPC) tissues and the EBV-positive cell line C666-1, the miR-BART family accounted for more than 10% of all detected miRNAs, suggesting that these miRNAs have important roles in maintaining latent EBV infections and in driving NPC tumorigenesis. In addition, EBV miRNA-based clustering analysis clearly distinguished between the three distinct EBV latency types, and our results suggested that a switch from type I to type III latency might occur in the Daudi BL cell line.ConclusionsOur data provide a comprehensive profiling of the EBV miRNA transcriptome that is associated with specific tumor cells in the three types of latent EBV infection states. EBV miRNA species represent a cluster of non-encoding latency biomarkers that are differentially expressed in tumor cells and may help to distinguish between the different latency types.
Highlights
Epstein-Barr virus (EBV) is an etiological cause of many human lymphocytic and epithelial malignancies
Quantitative analysis of viral-coding transcripts in EBVinfected cell lines and nasopharyngeal carcinoma (NPC) tissues The previous identification of the EBV latency types was mainly based on viral EBERs, nuclear antigens, LMP1, LMP2 and the Bam H1 rightward transcripts [2,22,23,24,25]
EBNA1 is expressed under the alternative promoters Wp, Cp and Qp in a latency type-specific manner [22,24,35], and LMP1 exhibits differential abundance when compared to the various latency types [1], suggesting that the activities of the three latency promoters that control EBNA1 expression and LMP1 abundance can characterize the three latency types
Summary
Epstein-Barr virus (EBV) is an etiological cause of many human lymphocytic and epithelial malignancies. EBV expresses different genes that are associated with three latency types. As many as 44 EBV-encoded miRNA species have been found, but their comprehensive profiles in the three types of latent infection that are associated with various types of tumors are not well documented. Increasing evidence suggests that EBV is an oncogenic human virus that causes many malignancies [1,2,3]. The comparable profiling of EBV miRNA transcriptomes in tumor cells in the three types of latency states has not been performed. We investigated the comprehensive expression patterns of EBV miRNA species in cells with different types of latency and emphasized the viral miRNA patterns in NPC tissues and cells in the EBV latency II state. Over the course of evolution, a subset of viruses, including the herpesviruses, has obtained the ability to hijack this antiviral mechanism of host cells to help maintain a persistent infection [13,14,15,16]
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