scholarly journals Genetics and Molecular Biology of Epstein-Barr Virus-Encoded BART MicroRNA: A Paradigm for Viral Modulation of Host Immune Response Genes and Genome Stability

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
David H. Dreyfus
Keyword(s):  
Immune Response ◽  
Genome Stability ◽  
Epstein Barr Virus ◽  
Host Immune Response ◽  
Barr Virus ◽  
Immune Response Genes ◽  
Human Immune Response ◽  
Human Immune ◽  
Bystander Cells ◽  
Epstein Barr

Epstein-Barr virus, a ubiquitous human herpesvirus, is associated through epidemiologic evidence with common autoimmune syndromes and cancers. However, specific genetic mechanisms of pathogenesis have been difficult to identify. In this review, the author summarizes evidence that recently discovered noncoding RNAs termed microRNA encoded by Epstein-Barr virus BARF (BamHI A right frame) termed BART (BamHI A right transcripts) are modulators of human immune response genes and genome stability in infected and bystander cells. BART expression is apparently regulated by complex feedback loops with the host immune response regulatory NF-κB transcription factors. EBV-encoded BZLF-1 (ZEBRA) protein could also regulate BART since ZEBRA contains a terminal region similar to ankyrin proteins such as IκBαthat regulate host NF-κB. BALF-2 (BamHI A left frame transcript), a viral homologue of the immunoglobulin and T cell receptor gene recombinase RAG-1 (recombination-activating gene-1), may also be coregulated with BART since BALF-2 regulatory sequences are located near the BART locus. Viral-encoded microRNA and viral mRNA transferred to bystander cells through vesicles, defective viral particles, or other mechanisms suggest a new paradigm in which bystander or hit-and-run mechanisms enable the virus to transiently or chronically alter human immune response genes as well as the stability of the human genome.

Deregulation of Immune Response Genes in Patients With Epstein-Barr Virus-Associated Gastric Cancer and Outcomes

2015 ◽  
Vol 148 (1) ◽  
pp. 137-147.e9 ◽  
Author(s):  
Sun Young Kim ◽  
Charny Park ◽  
Ha-Jung Kim ◽  
Jihyun Park ◽  
Jinha Hwang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immune Response ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Immune Response Genes ◽  
Epstein Barr

scholarly journals The Epstein-Barr Virus-Encoded LMP-1 Oncoprotein Negatively Affects Tyk2 Phosphorylation and Interferon Signaling in Human B Cells

2006 ◽  
Vol 80 (23) ◽  
pp. 11638-11650 ◽  
Author(s):  
Timothy R. Geiger ◽  
Jennifer M. Martin
Keyword(s):  
Immune Response ◽  
Persistent Infection ◽  
Epstein Barr Virus ◽  
Nuclear Translocation ◽  
Host Immune Response ◽  
Protein Levels ◽  
Barr Virus ◽  
Human B Cells ◽  
Signaling Domain ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) establishes a persistent infection in the human host and is associated with a variety of human cancers. Persistent infection results from a balance between the host immune response and viral immune evasion mechanisms. EBV infection is controlled initially by the innate immune response and later by T-cell-mediated adaptive immunity. EBV has evolved mechanisms to evade the host immune response so that it can persist for the lifetime of the host. Latent membrane protein 1 (LMP-1) is the EBV oncoprotein essential for B-cell immortalization by EBV. We show here that LMP-1 interacts with Tyk2, a signaling intermediate in the alpha interferon (IFN-α) signaling pathway, via a previously uncharacterized LMP-1 signaling domain. LMP-1 prevents Tyk2 phosphorylation and inhibits IFN-α-stimulated STAT2 nuclear translocation and interferon-stimulated response element transcriptional activity. Long-term culture of EBV+ lymphoblastoid cells in IFN-α is associated with outgrowth of a population expressing elevated LMP-1 protein levels, suggesting that cells expressing higher levels of LMP-1 survive the antiproliferative selective pressure imposed by IFN-α. These results show that LMP-1 can protect EBV+ cells from the IFN-α-stimulated antiviral/antiproliferative response and suggest that chronic IFN-α treatment may encourage the outgrowth of cells expressing elevated, and therefore potentially oncogenic, LMP-1 levels in EBV+ individuals.

scholarly journals Epstein-Barr Virus miR-BART6-3p Inhibits the RIG-I Pathway

2017 ◽  
Vol 9 (6) ◽  
pp. 574-586 ◽  
Author(s):  
Yuanjun Lu ◽  
Zailong Qin ◽  
Jia Wang ◽  
Xiang Zheng ◽  
Jianhong Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Epstein Barr Virus ◽  
Type I ◽  
Receptor Signaling ◽  
Viral Pathogen ◽  
Infection Period ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

Recognition of viral pathogen-associated molecular patterns by pattern recognition receptors (PRRs) is the first step in the initiation of a host innate immune response. As a PRR, RIG-I detects either viral RNA or replication transcripts. Avoiding RIG-I recognition is a strategy employed by viruses for immune evasion. Epstein-Barr virus (EBV) infects the majority of the human population worldwide. During the latent infection period there are only a few EBV proteins expressed, whereas EBV-encoded microRNAs, such as BART microRNAs, are highly expressed. BART microRNAs regulate both EBV and the host's gene expression, modulating virus proliferation and the immune response. Here, through gene expression profiling, we found that EBV miR-BART6-3ps inhibited genes of RIG-I-like receptor signaling and the type I interferon (IFN) response. We demonstrated that miR-BART6-3p rather than other BARTs specifically suppressed RIG-I-like receptor signaling-mediated IFN-β production. RNA-seq was used to analyze the global transcriptome change upon EBV infection and miR-BART6-3p mimics transfection, which revealed that EBV infection-triggered immune response signaling can be repressed by miR-BART6-3p overexpression. Furthermore, miR-BART6-3p inhibited the EBV-triggered IFN-β response and facilitated EBV infection through targeting the 3′UTR of RIG-I mRNA. These findings provide new insights into the mechanism underlying the strategies employed by EBV to evade immune surveillance.

scholarly journals THE VALUE OF THE IMMUNE RESPONSE IN PATIENTS WITH EBV INFECTIOUS MONONUCLEOSIS IN PREDICTING THE COURSE AND EFFICACY OF ANTIVIRAL AND IMMUNO IMMUNOCORRECTING THERAPY

2013 ◽  
Vol 18 (1) ◽  
pp. 7-14
Author(s):  
T. A. Svintsova ◽  
D. M. Sobchak ◽  
O. V. Korochkina ◽  
G. A Kravchenko ◽  
V. V Novikov
Keyword(s):  
Immune Response ◽  
Infectious Mononucleosis ◽  
Epstein Barr Virus ◽  
Mononuclear Cells ◽  
Polyclonal Antibodies ◽  
Severity Of Illness ◽  
Control Group ◽  
Differentiation Antigens ◽  
Barr Virus ◽  
Epstein Barr

The indices of immune response were studied in 68 patients with infectious mononucleosis caused by the Epstein-Barr virus (35 males, 33 females) aged 18 to 30 years. Materials and methods. The content of soluble forms of differentiation antigens (sCD95, sCD18, sCD50, sHLAI, sCD54) has been studied with enzyme immunoassay using monoclonal antibodies Mab IC0-20 and polyclonal antibodies to the antigens of the mononuclear cells of the peripheral blood. The control group included 60 healthy volunteers matched for age and sex with the main group. The aim of this study is the assessment of the content of soluble forms of differentiation antigens in patients with infectious mononucleosis caused by Epstein-Barr virus, depending on gender, age, severity of illness, comorbidities, laboratory values, the presence of viral DNA, as well as a demonstration of their value in predicting the course and outcome of the disease and the efficacy of antiviral and immunocorrecting therapy. In patients with negative results of DNA indication of EBV a significant increase in the content of soluble forms of differentiation antigens characterizing the adhesion of leukocytes (sCD18), the activity of T-lymphocytes (sCD50), the recognition of foreign antigens (sHLAI) in the blood in comparison with patients with a positive DNA indication of EBV was determined. Conclusion. According to the results of this performed work the criterion for an adequate immune response in patients with infectious mononucleosis caused by the Epstein-Barr virus was found to be the increase of the content of soluble forms of differentiation antigens (sCD95, sCD18, sCD50 sHLAI, sCD54). In patients with exanthema, tonsillar syndrome, leukocytosis, elevation of transaminases and the presence of antibodies to capsid antigen (a/VCAIgM) the content of soluble forms of differentiation antigens (sCD95, sCD18, sCD50 sHLAI, sCD54), was higher than in patients without such symptoms. In the treatment with cycloferon in patients with cyclic course of EBV infectious mononucleosis the content of sHLAI and sCD54 at 2nd-4th weeks of treatment increased by 1.5-2 times compared with the corresponding values before treatment. In patients with reactivation of the disease monotonically low indices of all studied soluble forms of differentiation antigens persisted over the 4 weeks during patients following up. In patients with infectious mononucleosis caused by Epstein-Barr virus, the dynamics of sHLAI and sCD54 after 2-4 weeks of treatment serves as secondary efficacy endpoint of antiviral, immunomodulatory therapy and the formation of the cyclic course of the disease.

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