Article

EBV microRNAs in primary lymphomas and targeting of CXCL-11 by ebv-mir-BHRF1-3

The Viral Oncology Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Cancer Research (Impact Factor: 9.33). 04/2008; 68(5):1436-42. DOI: 10.1158/0008-5472.CAN-07-5126
Source: PubMed

ABSTRACT

EBV-encoded microRNAs (miRNAs) have been identified and their functions are being studied. The expression pattern of these miRNAs in clinical samples of EBV-associated non-Hodgkin's lymphomas is unknown. We analyzed five primary "endemic" pediatric Burkitt's lymphomas (BL), two acquired immunodeficiency syndrome (AIDS)-related type I latency BL lines, a type III latency line, three EBV(+) primary effusion lymphomas (PEL), and three AIDS-related diffuse large B-cell lymphomas (DLBCL) for expression of EBV-encoded miRNAs. A markedly elevated expression of miRNA BHRF1-3 in type III relative to its parental type I BL line was found. Primary unmanipulated type I BLs and EBV(+) PELs expressed high levels of BART2 miRNA, whereas DLBCLs expressed both BART2 and BHRF1-3 species. BHRF1-3 miRNA expression inversely correlated with levels of a putative cellular target, the IFN-inducible T-cell attracting chemokine CXCL-11/I-TAC, and suppression of this factor was reversed by transfection of an antisense oligo to the EBV miRNA BHRF1-3. EBV-encoded miRNAs are expressed in primary lymphomas classically linked to the virus and are associated with the viral latency status. Targeted suppression of CXCL-11/I-TAC by a viral-encoded miRNA may serve as an immunomodulatory mechanism in these tumors.

Download full-text

Full-text

Available from: Ngoc Toomey, Apr 29, 2014
    • "During the early phase of B cell infection , BHRF1 microRNAs may induce apoptosis resistance and cell proliferation (Seto et al. 2010 ). In primary lymphomas exhibiting latency type III, miR-BHRF1-3 may contribute to the downregulation of the T cell attracting chemokine CXCL11 (Xia et al. 2008 ). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Latent Epstein-Bar virus genomes undergo epigenetic modifications which are dependent on the respective tissue type and cellular phenotype. These define distinct viral epigenotypes corresponding with latent viral gene expression profiles. Viral Latent Membrane Proteins 1 and 2A can induce cellular DNA methyltransferases, thereby influencing the methylation status of the viral and cellular genomes. Therefore, not only the viral genomes carry epigenetic modifications, but also the cellular genomes adopt major epigenetic alterations upon EBV infection. The distinct cellular epigenotypes of EBV-infected cells differ from the epigenotypes of their normal counterparts. In Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC) and EBV-associated gastric carcinoma (EBVaGC) significant changes in the host cell methylome with a strong tendency towards CpG island hypermethylation are observed. Hypermethylated genes unique for EBVaGC suggest the existence of an EBV-specific "epigenetic signature". Contrary to the primary malignancies carrying latent EBV genomes, lymphoblastoid cells (LCs) established by EBV infection of peripheral B cells in vitro are characterized by a massive genome-wide demethylation and a significant decrease and redistribution of heterochromatic histone marks. Establishing complete epigenomes of the diverse EBV-associated malignancies shall clarify their similarities and differences and further clarify the contribution of EBV to the pathogenesis, especially for the epithelial malignancies, NPC and EBVaGC.
    No preview · Article · Dec 2015 · Advances in Experimental Medicine and Biology
    • "Interestingly, cactus, which is an inhibitor of the Toll pathway, was positively regulated by aae-miR-375, whereas REL1, which is an activator of AMPs, was downregulated by the same miRNA. The increase in cactus and decrease in REL1 was found to have a positive effect on DENV replication since AMPs have been shown to negatively affect DENV (Luplertlop et al., 2012; Xia et al., 2008). Coincidence of negative regulation of AMPs upon blood feeding may provide a fitness advantage for the virus. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Insects are the most successful group of animals on earth, owing this partly to their very effective immune responses to microbial invasion. These responses mainly include cellular and humoral responses as well as RNA interference (RNAi). Small non-coding RNAs (snRNAs) produced through RNAi are important molecules in the regulation of gene expression in almost all living organisms; contributing to important processes such as development, differentiation, immunity as well as host-microorganism interactions. The main snRNAs produced by the RNAi response include short interfering RNAs, microRNAs and piwi-interacting RNAs. In addition to the host snRNAs, some microorganisms encode snRNAs that affect the dynamics of host-pathogen interactions. In this review, we will discuss the latest developments in regards to the role of microRNA in insect host-pathogen interactions and provide some insights into this rapidly developing area of research.
    No preview · Article · Aug 2014 · Journal of Insect Physiology
  • Source
    • "Several virus-encoded miRNAs have been reported to target host transcripts for their own advantage. There are reports of viral miRNAs targeting antiviral signaling molecules, e.g., EBV encoded miR-BHRF1-3 downregulates CXC-chemokine ligand 11 (CXCL11), an interferon (IFN)-inducible T-cell chemoattractant (Xia et al., 2008). The host gene Thrombospondin 1 (THBS1) has been reported to be targeted by multiple KSHV miRNAs, identified through gene expression profiling of cells engineered to stably express 10 KSHV pre-miRNAs (Samols et al., 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Host-virus interaction via host cellular components has been an important field of research in recent times. RNA interference mediated by short interfering RNAs and microRNAs (miRNA), is a widespread anti-viral defence strategy. Importantly, viruses also encode their own miRNAs. In recent times miRNAs were identified as key players in host-virus interaction. Furthermore, viruses were shown to exploit the host miRNA networks to suite their own need. The complex cross-talk between host and viral miRNAs and their cellular and viral targets forms the environment for viral pathogenesis. Apart from protein-coding mRNAs, non-coding RNAs may also be targeted by host or viral miRNAs in virus infected cells, and viruses can exploit the host miRNA mediated gene regulatory network via the competing endogenous RNA effect. A recent report showed that viral U-rich non-coding RNAs called HSUR, expressed in primate virus herpesvirus saimiri (HVS) infected T cells, were able to bind to three host miRNAs, causing significant alteration in cellular level for one of the miRNAs. We have predicted protein coding and non protein-coding targets for viral and human miRNAs in virus infected cells. We identified viral miRNA targets within host non-coding RNA loci from AGO interacting regions in three different virus infected cells. Gene ontology (GO) and pathway enrichment analysis of the genes comprising the ceRNA networks in the virus infected cells revealed enrichment of key cellular signalling pathways related to cell fate decisions and gene transcription, like Notch and Wnt signalling pathways, as well as pathways related to viral entry, replication and virulence. We identified a vast number of non-coding transcripts playing as potential ceRNAs to the immune response associated genes; e.g. APOBEC family genes, in some virus infected cells. All these information are compiled in HumanViCe, a comprehensive database that provides the potential ceRNA networks in virus infected human cells.
    Full-text · Article · Jul 2014 · Frontiers in Genetics
Show more