Epstein-Ban virus induction of recombinaseactivatina cenes RAG1 and RAG2

Department of Infectious Diseases and Virology, St. Jude's Children's Research Hospital, Memphis, Tennessee 38101-0318, USA.
Journal of Virology (Impact Factor: 4.44). 01/1996; 69(12):8155-8.
Source: PubMed


In experimental B-cell infections, Epstein-Barr virus induced sustained expression of V(D)J recombinase-activating genes RAG1 and RAG2, whose aberrant activity has been implicated in chromosomal translocations in B-cell neoplasms. In cell lines in which RAG1 and RAG2 were detected, virus integrated into cellular DNA rather than assumed the configuration of extrachromosomal episomes. Expression of the Epstein-Barr virus nuclear antigen 1 in transient transfection assays was sufficient to induce both recombinase-activating genes.

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    • "There are EBNA1 binding sites in the human genome and, as EBNA1 can bind both RNA and DNA, it could influence the expression of viral or cellular genes [75], possibly by eliciting demethylation and subsequent activation or dysfunction of cellular functions [59]. EBNA1 can up regulate the recombinase-activating genes which mediate V-D-J combination and are usually only expressed in immature lymphoid cells [76]. EBNA1 is indispensable for B cell transformation and can enhance B cell immortalization several thousandfold [77]. "
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    ABSTRACT: Certain infectious agents are associated with lymphomas, but the strength of the association varies geographically, suggesting that local environmental factors make important contributions to lymphomagenesis. Endemic Burkitt's Lymphoma has well-defined environmental requirements making it particularly suitable for research into local environmental factors. The Epstein-Barr virus and holoendemic Malaria are recognized as important cofactors in endemic Burkitt's Lymphoma and their contributions are discussed. Additionally, infection with Chikungunya Fever, a potentially oncogenic arbovirus, was associated with the onset of endemic Burkitt's Lymphoma in one study and also with space-time case clusters of the lymphoma. Chikungunya Virus has several characteristics typical of oncogenic viruses. The Flavivirus, Hepatitis C, a Class 1 Human Carcinogen, closely related to the arboviruses, Yellow Fever, and Dengue, is also more distantly related to Chikungunya Virus. The mechanisms of oncogenesis believed to operate in Hepatitis C lymphomagenesis are discussed, as is their potential applicability to Chikungunya Virus.
    Full-text · Article · Jan 2012 · Advances in Hematology
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    • "EBNA1 has been shown to bind to their promoters (O'Neil et al., 2008). In addition, EBNA1 increases expression of the V(D)J recombinases RAG1 and RAG2 (Srinivas and Sixbey, 1995). These findings suggest that EBNA1 might facilitate recombination events and could thereby contribute to the c-myc (Ig) locus translocation that is crucial for the development of BL. "
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    ABSTRACT: Epstein-Barr virus (EBV) is widely spread in the human population. EBV nuclear antigen 1 (EBNA1) is a transcription factor that activates viral genes and is necessary for viral replication and partitioning, which binds the EBV genome cooperatively. We identify similar EBNA1 repeat binding sites in the human genome using a nearest-neighbor positional weight matrix. Previously experimentally verified EBNA1 sites in the human genome are successfully recovered by our approach. Most importantly, 40 novel regions are identified in the human genome, constituted of tandemly repeated binding sites for EBNA1. Genes located in the vicinity of these regions are presented as possible targets for EBNA1-mediated regulation. Among these, four are discussed in more detail: IQCB1, IMPG1, IRF2BP2 and TPO. Incorporating the cooperative actions of EBNA1 is essential when identifying regulatory regions in the human genome and we believe the findings presented here are highly valuable for the understanding of EBV-induced phenotypic changes.
    Full-text · Article · Sep 2010 · Virology
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    • "However, in support of a role for EBNA1 in carcinogenesis we and others have demonstrated that EBNA1's transcription factor-like functions are not confined to the regulation of viral genes but also extend to the regulation of host cell gene expression. This has been demonstrated in the context of B-cells where EBNA1 has been shown to induce the expression of CD25, RAG1, RAG2 and CCL20 [10-12] whilst in epithelial cells we have established that expression of EBNA1 results in the differential regulation of cellular genes involved in translation, transcription and cell signalling [13,14]. We have documented that EBNA1 enhances STAT1 expression which sensitises cells to interferon-induced STAT1 activation, modulates signalling in the TGFβ1 pathway, and increases AP-1 activity resulting in the enhancement of host cell mechanisms involved in angiogenesis and metastasis [13,14]. "
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