scholarly journals Essential role of hyperacetylated microtubules in innate immunity escape orchestrated by the EBV-encoded BHRF1 protein

2021 ◽  
Author(s):  
Damien Glon ◽  
G&eacuteraldine Vilmen ◽  
Daniel Perdiz ◽  
Eva Hernandez ◽  
Guillaume Beauclair ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Signaling Pathway ◽  
Mitochondrial Dynamics ◽  
Virus Reactivation ◽  
Post Translational Modifications ◽  
Barr Virus ◽  
Tubulin Acetylation ◽  
Epstein Barr ◽  
Aggresome Formation

Innate immunity constitutes the first line of defense against viruses, in which mitochondria play an important role in the induction of the interferon (IFN) response. BHRF1, a multifunctional viral protein expressed during Epstein-Barr virus reactivation, modulates mitochondrial dynamics and disrupts the IFN signaling pathway. Mitochondria are mobile organelles that move through the cytoplasm thanks to the cytoskeleton and in particular the microtubule (MT) network. MTs undergo various post-translational modifications, among them tubulin acetylation. In this study, we demonstrated that BHRF1 induces MT hyperacetylation to escape innate immunity. Indeed, expression of BHRF1 induces the aggregation of shortened mitochondria next to the nucleus. This mito-aggresome is organized around the centrosome and its formation is MT-dependent. We also observed that the BHRF1-induced hyperacetylation of MTs involves the α-tubulin acetyltransferase ATAT1. Thanks to a non-acetylatable α-tubulin mutant, we demonstrated that this hyperacetylation is necessary for the mito-aggresome formation. We investigated the mechanism leading to the clustering of mitochondria, and we identified dyneins as motors that are required for the mitochondrial aggregation. Finally, we demonstrated that BHRF1 needs MT hyperacetylation to block the induction of the IFN response. Indeed, in the absence of MT hyperacetylation, BHRF1 is unable to initiate the sequestration of mitochondria into autophagosomes, and mitophagy, which is essential to inhibiting the signaling pathway. Therefore, our results reveal the role of the MT network, and its acetylation level, in the induction of a pro-viral mitophagy.

Are Viruses and Parasites Linked to Celiac Disease? A Question that Still has no Definite Answer

2019 ◽  
Vol 20 (14) ◽  
pp. 1181-1193 ◽  
Author(s):  
Aref Shariati ◽  
Hamid R. Aslani ◽  
Mohammad R.H. Shayesteh ◽  
Ali Taghipour ◽  
Ahmad Nasser ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Multiple Roles ◽  
Barr Virus ◽  
The People ◽  
Intestinal Infections ◽  
Inflammatory Bowel ◽  
Epstein Barr ◽  
Irritable Bowel ◽  
Related Proteins

Celiac Disease (CD) is a complex autoimmune enteropathy of the small intestine that commonly occurs in genetically predisposed individuals due to intake of gluten and related proteins. Gluten consumption, duration of breast-feeding, various infections, especially frequent intestinal infections, vaccinations and use of antibiotics can be linked to CD. It is predicted that it affects 1% of the global population and its incidence rate is increasing. Most of the people with the HLA-DQ2 or HLADQ8 are at a higher risk of developing this disease. The link between infections and autoimmune diseases has been very much considered in recent years. In several studies, we explained that pathogenic and non-pathogenic microorganisms might have multiple roles in initiation, exacerbation, and development of Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD). In various studies, the relationship between infections caused by viruses, such as Epstein-Barr Virus (EBV), Rotavirus, Hepatitis C (HCV), Hepatitis B virus (HBV), Cytomegalovirus (CMV), and Influenza virus, and parasites including Giardia spp. and Toxoplasma gondii with CD has been raised. However, increasing evidence proposes that some of these microorganisms, especially helminths, can also have protective and even therapeutic roles in the CD process. Therefore, in order to determine the role of microorganisms in the process of this disease, we attempted to summarize the evidence suggesting the role of viral and parasitic agents in pathogenesis of CD.

Valganciclovir suppressed Epstein Barr virus reactivation during immunosuppression with alemtuzumab

2014 ◽  
Vol 59 (4) ◽  
pp. 255-258 ◽  
Author(s):  
Harinder Gill ◽  
Yu-Yan Hwang ◽  
Thomas S.Y. Chan ◽  
Annie W.K. Pang ◽  
Anskar Y.H. Leung ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Virus Reactivation ◽  
Barr Virus ◽  
Epstein Barr ◽  
Epstein Barr Virus Reactivation

scholarly journals PIAS1 potentiates the anti-EBV activity of SAMHD1 through SUMOylation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Farjana Saiada ◽  
Kun Zhang ◽  
Renfeng Li
Keyword(s):  
Lytic Replication ◽  
Dependent Manner ◽  
Dna Viruses ◽  
Post Translational Modifications ◽  
Protein Protein Interaction ◽  
Barr Virus ◽  
Sumo Ligase ◽  
Lysine Residues ◽  
Epstein Barr ◽  
Rna And Dna

Abstract Background Sterile alpha motif and HD domain 1 (SAMHD1) is a deoxynucleotide triphosphohydrolase (dNTPase) that restricts the infection of a variety of RNA and DNA viruses, including herpesviruses. The anti-viral function of SAMHD1 is associated with its dNTPase activity, which is regulated by several post-translational modifications, including phosphorylation, acetylation and ubiquitination. Our recent studies also demonstrated that the E3 SUMO ligase PIAS1 functions as an Epstein-Barr virus (EBV) restriction factor. However, whether SAMHD1 is regulated by PIAS1 to restrict EBV replication remains unknown. Results In this study, we showed that PIAS1 interacts with SAMHD1 and promotes its SUMOylation. We identified three lysine residues (K469, K595 and K622) located on the surface of SAMHD1 as the major SUMOylation sites. We demonstrated that phosphorylated SAMHD1 can be SUMOylated by PIAS1 and SUMOylated SAMHD1 can also be phosphorylated by viral protein kinases. We showed that SUMOylation-deficient SAMHD1 loses its anti-EBV activity. Furthermore, we demonstrated that SAMHD1 is associated with EBV genome in a PIAS1-dependent manner. Conclusion Our study reveals that PIAS1 synergizes with SAMHD1 to inhibit EBV lytic replication through protein–protein interaction and SUMOylation.

scholarly journals Molecular Genetics in Epstein–Barr Virus-Associated Malignancies

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 593
Author(s):  
Srikanth Umakanthan ◽  
Maryann M Bukelo
Keyword(s):  
Epstein Barr Virus ◽  
Diagnostic Tools ◽  
Main Role ◽  
Genetic Changes ◽  
Barr Virus ◽  
Cancer Pathogenesis ◽  
Genomic Studies ◽  
Epstein Barr ◽  
Oncogenic Form

Global genomic studies have detected the role of genomic alterations in the pathogenesis of Epstein–Barr virus (EBV)-associated tumors. EBV oncoproteins cause a vital shift of EBV from an infectious virus to an oncogenic form during the latent and lytic phase within the lymphoid B cells and epithelial cells. This epigenetic alteration modulates the virus and host genomes and inactivates and disrupts numerous tumor suppressors and signaling pathways. Genomic profiling has played the main role in identifying EBV cancer pathogenesis and its related targeted therapies. This article reviews the role of genetic changes in EBV-associated lymphomas and carcinomas. This includes the prolific molecular genesis, key diagnostic tools, and target-specific drugs that have been in recent clinical use.

EBV load is associated with cfDNA fragmentation and renal damage in SLE patients

Lupus ◽  
2021 ◽  
pp. 096120332110103
Author(s):  
Anna Truszewska ◽  
Agnieszka Wirkowska ◽  
Kamila Gala ◽  
Piotr Truszewski ◽  
Łucja Krzemień-Ojak ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Lupus Erythematosus ◽  
Epstein Barr Virus ◽  
Renal Damage ◽  
Healthy Individuals ◽  
Pcr Assay ◽  
Barr Virus ◽  
Fragmentation Index ◽  
Epstein Barr

Background For long Epstein–Barr virus (EBV) has been suspected to be involved in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to verify the association between EBV, cell-free DNA (cfDNA) and kidney disease in SLE. Methods Blood samples were obtained from 43 SLE patients and 50 healthy individuals. EBV load was measured via real-time PCR assay. Sizing and quantification of plasma cfDNA was performed on Bioanalyzer. We proposed that the uniformity of cfDNA fragmentation can be described using cfDNA fragmentation index. Results SLE patients with chronic kidney disease (CKD +) had higher EBV load compared to CKD(–) patients (P = 0.042). Patients with high cfDNA level had higher EBV load (P = 0.041) and higher cfDNA fragmentation index (P < 0.001) compared to patients with low cfDNA level. Among patients with high cfDNA level, EBV load was higher in CKD(+) group compared to CKD(–) group (P = 0.035). EBV load was positively correlated with the fragmentation index in all SLE patients (P = 0.028, R2 = 0.13), and the correlation was even more pronounced in CKD (+) patients (P < 0.001, R2 = 0.20). Conclusions We showed that EBV load was associated with non-uniform cfDNA fragmentation, higher cfDNA levels, and kidney disease in SLE patients. Although the causality of this relationship could not be determined with the current study, it brings rationale for further investigations on the role of EBV and cfDNA interplay in SLE pathogenesis.

scholarly journals Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: The Human Herpesviruses Are Back!

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 185
Author(s):  
Maria Eugenia Ariza
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Disease Process ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Barr Virus ◽  
Fatigue Syndrome ◽  
Specific Proteins ◽  
Epstein Barr ◽  
Human Herpesviruses

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or Systemic Exertion Intolerance Disease (SEID) is a chronic multisystem illness of unconfirmed etiology. There are currently no biomarkers and/or signatures available to assist in the diagnosis of the syndrome and while numerous mechanisms have been hypothesized to explain the pathology of ME/CFS, the triggers and/or drivers remain unknown. Initial studies suggested a potential role of the human herpesviruses especially Epstein-Barr virus (EBV) in the disease process but inconsistent and conflicting data led to the erroneous suggestion that these viruses had no role in the syndrome. New studies using more advanced approaches have now demonstrated that specific proteins encoded by EBV could contribute to the immune and neurological abnormalities exhibited by a subgroup of patients with ME/CFS. Elucidating the role of these herpesvirus proteins in ME/CFS may lead to the identification of specific biomarkers and the development of novel therapeutics.

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