scholarly journals Structural and Biophysical Investigation of the Key Hotspots on the Surface of Epstein–Barr Nuclear Antigen 1 Essential for DNA Recognition and Pathogenesis

2021 ◽  
Vol 8 ◽  
Author(s):  
Huma Farooque Hashmi ◽  
Muhammad Waseem ◽  
Syed Shujait Ali ◽  
Zahid Hussain ◽  
Kaoshan Chen
Keyword(s):  
Binding Affinity ◽  
Drug Target ◽  
Critical Role ◽  
Nuclear Antigen ◽  
Total Binding Energy ◽  
Barr Virus ◽  
Design Structure ◽  
Epstein Barr ◽  
The Impact ◽  
Epstein Barr Nuclear Antigen

Epstein-Barr Virus (EBV) is considered the most important human pathogen due to its role in infections and cellular malignancies. It has been reported that this Oncolytic virus infects 90% world’s population. EBNA1 is required for DNA binding and survival of the virus and is considered an essential drug target. The biochemical and structural properties of this protein are known, but it is still unclear which residues impart a critical role in the recognition of dsDNA. Intending to disclose only the essential residues in recognition of dsDNA, this study used a computational pipeline to generate an alanine mutant of each interacting residue and determine the impact on the binding. Our analysis revealed that R469A, K514A, Y518A, R521A and R522A are the key hotspots for the recognition of dsDNA by the EBNA1. The dynamics properties, i.e. stability, flexibility, structural compactness, hydrogen bonding frequency, binding affinity, are altered by disrupting the protein-DNA contacts, thereby decreases the binding affinity. In particular, the two arginine substitution, R521A and R522A, significantly affected the total binding energy. Thus, we hypothesize that these residues impart a critical role in the dsDNA recognition and pathogenesis. This study would help to design structure-based drugs against the EBV infections.

HAUSP/USP7 as an Epstein–Barr virus target

2004 ◽  
Vol 32 (5) ◽  
pp. 731-732 ◽  
Author(s):  
M.N. Holowaty ◽  
L. Frappier
Keyword(s):  
Epstein Barr Virus ◽  
Latent Infection ◽  
Nuclear Antigen ◽  
Barr Virus ◽  
High Affinity ◽  
Cellular Immortalization ◽  
Epstein Barr ◽  
Epstein Barr Nuclear Antigen

USP7 (also called HAUSP) is a de-ubiquitinating enzyme recently identified as a key regulator of the p53–mdm2 pathway, which stabilizes both p53 and mdm2. We have discovered that the Epstein–Barr nuclear antigen 1 protein of Epstein–Barr virus binds with high affinity to USP7 and disrupts the USP7–p53 interaction. The results have important implications for the role of Epstein–Barr nuclear antigen 1 in the cellular immortalization that is typical of an Epstein–Barr virus latent infection.

scholarly journals Genotypic Characterization of Epstein Barr Virus in Blood of Patients with Suspected Nasopharyngeal Carcinoma in Ghana

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 766
Author(s):  
Richmond Ayee ◽  
Maame Ekua Oforiwaa Ofori ◽  
Emmanuel Ayitey Tagoe ◽  
Sylvester Languon ◽  
Kafui Searyoh ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Venous Blood ◽  
Nasopharyngeal Cancer ◽  
Nuclear Antigen ◽  
Control Group ◽  
Barr Virus ◽  
Genotype 2 ◽  
Epstein Barr ◽  
Study Participants ◽  
Epstein Barr Nuclear Antigen

Nasopharyngeal cancer (NPC) is associated with Epstein Barr virus (EBV) infection. However different viral strains have been implicated in NPC worldwide. This study aimed to detect and characterize EBV in patients diagnosed with NPC in Ghana. A total of 55 patients diagnosed with NPC by CT scan and endoscopy were age-matched with 53 controls without a known oncological disease. Venous blood was collected from the study participants and DNA extracted from the blood samples. Detection of EBV and genotyping were done by amplifying Epstein Barr nuclear antigen 1 (EBNA-1) and Epstein Barr nuclear antigen 2 (EBNA-2), respectively, using specific primers. Viral load in patients and controls was determined using real-time polymerase chain reaction. EBV positivity in controls (92%) was significantly greater than that of NPC patients (67%) (χ2 = 19.17, p < 0.0001), and viral infection was independent of gender (χ2 = 1.770, p = 0.1834). The predominant EBV genotypes in patients and controls were genotype 2 (52%) and genotype 1 (62%), respectively. Median EBV load was significantly higher in NPC patients than the control group (p < 0.01). In summary, prevalence of EBV genotype 2 infection was higher in NPC patients than the control group. Assessment of EBV load may be used as a biomarker for the diagnosis of NPC.

The interaction between smoking and Epstein-Barr virus as multiple sclerosis risk factors may depend on age

2013 ◽  
Vol 20 (6) ◽  
pp. 747-750 ◽  
Author(s):  
Jonatan Salzer ◽  
Hans Stenlund ◽  
Peter Sundström
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Epstein Barr Virus ◽  
Nuclear Antigen ◽  
Positive Interaction ◽  
Barr Virus ◽  
Older Subjects ◽  
Epstein Barr ◽  
A Prospective Study ◽  
Epstein Barr Nuclear Antigen

The multiple sclerosis (MS) risk factors smoking and remote Epstein-Barr virus (EBV) infection have been suggested to interact statistically, but the results are conflicting. In a prospective study on 192 MS cases and 384 matched controls, we analysed levels of cotinine as a marker of smoke exposure, and Epstein-Barr Nuclear Antigen-1 antibody reactivity. We assessed interaction on the additive and multiplicative scales, and estimated the effects of the risk factors across strata of each other. The results suggest that a negative interaction may be present in samples drawn at a young age, and a positive interaction among older subjects.

scholarly journals Epigenetic reprogramming sensitizes immunologically silent EBV+ lymphomas to virus-directed immunotherapy

Blood ◽  
2020 ◽  
Vol 135 (21) ◽  
pp. 1870-1881 ◽  
Author(s):  
Tanner Dalton ◽  
Ekaterina Doubrovina ◽  
Dmitry Pankov ◽  
Raymond Reynolds ◽  
Hanna Scholze ◽  
...  
Keyword(s):  
T Cell ◽  
Cytotoxic T Cells ◽  
Nuclear Antigen ◽  
Potent Inducer ◽  
Barr Virus ◽  
Cell Immunotherapy ◽  
T Cell Homing ◽  
Inhibition Of Tumor Growth ◽  
Epstein Barr ◽  
Epstein Barr Nuclear Antigen

Abstract Despite advances in T-cell immunotherapy against Epstein-Barr virus (EBV)-infected lymphomas that express the full EBV latency III program, a critical barrier has been that most EBV+ lymphomas express the latency I program, in which the single Epstein-Barr nuclear antigen (EBNA1) is produced. EBNA1 is poorly immunogenic, enabling tumors to evade immune responses. Using a high-throughput screen, we identified decitabine as a potent inducer of immunogenic EBV antigens, including LMP1, EBNA2, and EBNA3C. Induction occurs at low doses and persists after removal of decitabine. Decitabine treatment of latency I EBV+ Burkitt lymphoma (BL) sensitized cells to lysis by EBV-specific cytotoxic T cells (EBV-CTLs). In latency I BL xenografts, decitabine followed by EBV-CTLs results in T-cell homing to tumors and inhibition of tumor growth. Collectively, these results identify key epigenetic factors required for latency restriction and highlight a novel therapeutic approach to sensitize EBV+ lymphomas to immunotherapy.

scholarly journals Epstein-Barr virus nuclear antigen 2 (EBNA2) extensively rewires the human chromatin landscape at autoimmune risk loci

2020 ◽  
Author(s):  
Ted Hong ◽  
Omer Donmez ◽  
Daniel Miller ◽  
Carmy Forney ◽  
Michael Lape ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Human Genome ◽  
Genetic Risk ◽  
Epstein Barr Virus ◽  
Critical Role ◽  
Chromatin Accessibility ◽  
Nuclear Antigen ◽  
Barr Virus ◽  
Chromatin Looping ◽  
Epstein Barr

AbstractThe interplay between environmental and genetic factors plays a key role in the development of many autoimmune diseases. In particular, the Epstein-Barr virus (EBV) is an established contributor to multiple sclerosis, lupus, and other disorders. Previously, we demonstrated that the EBV nuclear antigen 2 (EBNA2) transactivating protein occupies up to half of the risk loci for a set of seven autoimmune disorders. To further examine the mechanistic roles played by EBNA2 at these loci on genome-wide scale, we globally examined gene expression, chromatin accessibility, chromatin looping, and EBNA2 binding, in a B cell line that was 1) uninfected, 2) infected with a strain of EBV lacking EBNA2, or 3) infected with a strain that expresses EBNA2. We identified >400 EBNA2-dependent differentially expressed human genes and >4,000 EBNA2 binding events in the human genome. ATAC-seq analysis revealed >3,000 regions in the human genome with EBNA2-dependent chromatin accessibility, and HiChIP-seq data revealed >2,000 regions where EBNA2 altered chromatin looping interactions. Importantly, autoimmune genetic risk loci were highly enriched at the sites of these EBNA2-dependent chromatin-altering events. We present examples of autoimmune risk genotype-dependent EBNA2 events, nominating genetic risk mechanisms for autoimmune risk loci such as ZMIZ1 and CD80. Taken together, our results reveal important interactions between host genetic variation and EBNA2-driven disease mechanisms. Further, our study highlights a critical role for EBNA2 in rewiring human gene regulatory programs through rearrangement of the chromatin landscape and nominates these interactions as components of genetic mechanisms that influence the risk of multiple autoimmune diseases.

Simple repeat array in Epstein-Barr virus DNA encodes part of the Epstein-Barr nuclear antigen

Science ◽  
1983 ◽  
Vol 220 (4604) ◽  
pp. 1396-1398 ◽  
Author(s):  
K Hennessy ◽  
M Heller ◽  
V van Santen ◽  
E Kieff
Keyword(s):  
Epstein Barr Virus ◽  
Nuclear Antigen ◽  
Repeat Array ◽  
Simple Repeat ◽  
Barr Virus ◽  
Epstein Barr ◽  
Epstein Barr Nuclear Antigen
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