Abstract
Epstein–Barr virus (EBV) is a human γ-herpesvirus implicated in several human malignancies, including a wide range of lymphomas. Several molecules encoded by EBV in its latent state are believed to be related to EBV-induced lymphomagenesis, among which microRNAs—small RNAs with a posttranscriptional regulating role—are of great importance. The genome of EBV encodes 44 mature microRNAs belonging to two different classes, including BamHI-A rightward transcript (BART) and Bam HI fragment H rightward open reading frame 1 (BHRF1), with different expression levels in different EBV latency types. These microRNAs might contribute to the pathogenetic effects exerted by EBV through targeting self mRNAs and host mRNAs and interfering with several important cellular mechanisms such as immunosurveillance, cell proliferation, and apoptosis. In addition, EBV microRNAs can regulate the surrounding microenvironment of the infected cells through exosomal transportation. Moreover, these small molecules could be potentially used as molecular markers. In this review, we try to present an updated and extensive view of the role of EBV-encoded miRNAs in human lymphomas.
Highlights
Like other members of the herpesvirus family, Epstein–Barr virus (EBV) displays different patterns of gene expression, which are known as latency programs [12,13]
Regarding the topic of this review, i.e., the two families of microRNAs encoded by EBV (BamHI-A rightward transcript or BART; BamHI fragment H rightward open reading frame 1 or BHRF1), there are some differences in their expression patterns between different latency types (Table 1)
The BamHI W promoter (Wp)-restricted latency program was found in a subset of Burkitt lymphoma (BL), where a deletion of the EBNA2 gene in the viral genome led to the expression of EBNA1 and EBNA3s, granting the infected cells an elevated resistance to apoptosis [21,22]
Summary
It is believed that viruses contribute to 15–20% of human malignancies [1]. Among the discovered oncoviruses to date, Epstein–Barr Virus (EBV), which is named human herpesvirus 4 (HHV-4), is a key player in human malignancies [2]. Based on the expression patterns of the main EBV latent proteins, several latency programs have been described for the virus (Table 1) These latent proteins include EBV-encoded nuclear antigen 1 (EBNA1), EBNA2, EBNA3s (3A, 3B and 3C), latent membrane protein (LMP1), and LMP-2s (A and B) [18,19]. BART: BamHI-A rightward transcript; BHRF1: BamHI fragment H rightward open reading frame 1; BL: Burkitt lymphoma; CLL: chronic lymphocytic leukemia; DLBC: diffuse large B-cell lymphoma; EBER: EBV-encoded small RNA; EBNA: EBV-encoded nuclear antigen; HIV-DLBCL: HIV-related diffuse large B-cell lymphoma; HL: Hodgkin lymphoma; LCL: lymphoblastoid cell line; LMP: latent membrane protein; MTX-LPD: methotrexate-associated lymphoproliferative disorder; NKTL: natural killer/T-cell lymphoma; PAL: pyothorax-associated lymphoma; PBL: plasmablastic lymphoma; PTLD: post-transplant lymphoproliferative disorder
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