scholarly journals Epstein-Barr Virus Promotes the Production of Inflammatory Cytokines in Gingival Fibroblasts and RANKL-Induced Osteoclast Differentiation in RAW264.7 Cells

2022 ◽  
Vol 23 (2) ◽  
pp. 809
Author(s):  
Sho Yokoe ◽  
Akira Hasuike ◽  
Norihisa Watanabe ◽  
Hideki Tanaka ◽  
Hiroyuki Karahashi ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Epstein Barr Virus ◽  
Osteoclast Differentiation ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Dependent Manner ◽  
Gingival Fibroblasts ◽  
Virus Family ◽  
Barr Virus ◽  
Epstein Barr

Periodontitis is an inflammatory condition that causes the destruction of the supporting tissues of teeth and is a major public health problem affecting more than half of the adult population worldwide. Recently, members of the herpes virus family, such as the Epstein–Barr virus (EBV), have been suggested to be involved in the etiology of periodontitis because bacterial activity alone does not adequately explain the clinical characteristics of periodontitis. However, the role of EBV in the etiology of periodontitis is unknown. This study aimed to examine the effect of inactivated EBV on the expression of inflammatory cytokines in human gingival fibroblasts (HGFs) and the induction of osteoclast differentiation. We found that extremely high levels of interleukin (IL)-6 and IL-8 were induced by inactivated EBV in a copy-dependent manner in HGFs. The levels of IL-6 and IL-8 in HGFs were higher when the cells were treated with EBV than when treated with lipopolysaccharide and lipoteichoic acid. EBV induced IκBα degradation, NF-κB transcription, and RAW264.7 cell differentiation into osteoclast-like cells. These findings suggest that even without infecting the cells, EBV contributes to inflammatory cytokine production and osteoclast differentiation by contact with oral cells or macrophage lineage, resulting in periodontitis onset and progression.

DNA sequence heterogeneity within the Epstein–Barr virus family of repeats in the latent origin of replication

Gene ◽  
2001 ◽  
Vol 265 (1-2) ◽  
pp. 165-173 ◽  
Author(s):  
Alberto Fruscalzo ◽  
Giulia Marsili ◽  
Vincenzo Busiello ◽  
Luisa Bertolini ◽  
Domenico Frezza
Keyword(s):  
Dna Sequence ◽  
Epstein Barr Virus ◽  
Origin Of Replication ◽  
Virus Family ◽  
Sequence Heterogeneity ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals The Late Lytic LMP-1 Protein of Epstein-Barr Virus Can Negatively Regulate LMP-1 Signaling

2000 ◽  
Vol 74 (2) ◽  
pp. 1057-1060 ◽  
Author(s):  
Kimberly D. Erickson ◽  
Jennifer M. Martin
Keyword(s):  
Epstein Barr Virus ◽  
Lytic Cycle ◽  
Dependent Manner ◽  
Reading Frame ◽  
Barr Virus ◽  
Tetradecanoyl Phorbol Acetate ◽  
Human B Cells ◽  
Negative Effect ◽  
Epstein Barr ◽  
Related Proteins

ABSTRACT The BNLF-1 open reading frame of Epstein-Barr virus (EBV) encodes two related proteins, latent membrane protein-1 (LMP-1) and lytic LMP-1 (lyLMP-1). LMP-1 is a latent protein required for immortalization of human B cells by EBV, whereas lyLMP-1 is expressed during the lytic cycle and is found in the EBV virion. We show here that, in contrast to LMP-1, lyLMP-1 is stable, with a half-life of >20 h in tetradecanoyl phorbol acetate- and butyrate-treated B95-8 cells. Although lyLMP-1 itself has negligible effects on NF-κB activity, it inhibits NF-κB activation by LMP-1 in a dose-dependent manner. The lyLMP-1 protein does not oligomerize with LMP-1, and the negative effect of lyLMP-1 on NF-κB activation by LMP-1 does not result from lyLMP-1-mediated disruption of LMP-1 oligomers. Modulation of LMP-1-activated signaling pathways is the first identified biological activity associated with lyLMP-1, and this activity may contribute to the progression of EBV's lytic cycle.

scholarly journals Cell Cycle Association of the Retinoblastoma Protein Rb and the Histone Demethylase LSD1 with the Epstein-Barr Virus Latency Promoter Cp

2008 ◽  
Vol 82 (7) ◽  
pp. 3428-3437 ◽  
Author(s):  
Charles M. Chau ◽  
Zhong Deng ◽  
Hyojueng Kang ◽  
Paul M. Lieberman
Keyword(s):  
Cell Cycle ◽  
Epstein Barr Virus ◽  
Affinity Purification ◽  
Histone H3 ◽  
Histone Demethylase ◽  
Stable Complex ◽  
Dependent Manner ◽  
Barr Virus ◽  
A Cell ◽  
Epstein Barr

ABSTRACT The Epstein-Barr virus C promoter (Cp) regulates the major multicistronic transcript encoding the EBNA-LP, 1, 2, and 3 genes required for B-cell proliferation during latency. The growth-transforming potential of these viral genes suggests that they must be tightly regulated with the host cell cycle and differentiation process. To better understand Cp regulation, we used DNA affinity purification to identify cellular and viral proteins that bind to Cp in latently infected cells. Several previously unknown factors were identified, including the cell cycle regulatory proteins E2F1 and Rb. E2F1 bound to a specific site in Cp located in the core Cp region 3′ of the known EBNA2-responsive RBP-Jk (CSL, CBF1) binding site. The histone H3 K4 demethylase LSD1 (BCC110) was also identified by DNA affinity and was shown to form a stable complex with Rb. Coimmunoprecipitation assays demonstrated that E2F1, Rb, and LSD1 bind to Cp in a cell cycle-dependent manner. Rb and LSD1 binding to Cp increased after the S phase, corresponding to a decrease in histone H3 K4 methylation and Cp transcription. Coimmunoprecipitation and immunofluorescence assays reveal that LSD1 interacts with Rb. Surprisingly, LSD1 did not coimmunoprecipitate with E2F1, suggesting that it associates with Rb independently of E2F1. Depletion of LSD1 by small interfering RNAs inhibited Cp basal transcription levels, and overexpression of LSD1 altered the cell cycle profile in p53-positive (p53+), but not p53-negative (p53−), HCT cells. These findings indicate that Cp is a cell cycle-regulated promoter that is under the control of Rb and the histone demethylase LSD1 in multiple latency types.

scholarly journals Either ZEB1 or ZEB2/SIP1 Can Play a Central Role in Regulating the Epstein-Barr Virus Latent-Lytic Switch in a Cell-Type-Specific Manner

2010 ◽  
Vol 84 (12) ◽  
pp. 6139-6152 ◽  
Author(s):  
Amy L. Ellis ◽  
Zhenxun Wang ◽  
Xianming Yu ◽  
Janet E. Mertz
Keyword(s):  
Cell Lines ◽  
Epstein Barr Virus ◽  
Cellular Protein ◽  
Lytic Replication ◽  
Viral Reactivation ◽  
Dependent Manner ◽  
Cell Type ◽  
Barr Virus ◽  
A Cell ◽  
Epstein Barr

ABSTRACT We previously reported that the cellular protein ZEB1 can repress expression of the Epstein-Barr virus (EBV) BZLF1 gene in transient transfection assays by directly binding its promoter, Zp. We also reported that EBV containing a 2-bp substitution mutation in the ZEB-binding ZV element of Zp spontaneously reactivated out of latency into lytic replication at a higher frequency than did wild-type EBV. Here, using small interfering RNA (siRNA) and short hairpin RNA (shRNA) technologies, we definitively show that ZEB1 is, indeed, a key player in maintaining EBV latency in some epithelial and B-lymphocytic cell lines. However, in other EBV-positive epithelial and B-cell lines, another zinc finger E-box-binding protein, ZEB2/SIP1, is the key player. Both ZEB1 and ZEB2 can bind Zp via the ZV element. In EBV-positive cells containing only ZEB1, knockdown of ZEB1 led to viral reactivation out of latency, with synthesis of EBV immediate-early and early lytic gene products. However, in EBV-positive cells containing both ZEBs, ZEB2, not ZEB1, was the primary ZEB family member bound to Zp. Knockdown of ZEB2, but not ZEB1, led to EBV lytic reactivation. Thus, we conclude that either ZEB1 or ZEB2 can play a central role in the maintenance of EBV latency, doing so in a cell-type-dependent manner.

scholarly journals Epstein–Barr virus-infected cells release Fas ligand in exosomal fractions and induce apoptosis in recipient cells via the extrinsic pathway

2015 ◽  
Vol 96 (12) ◽  
pp. 3646-3659 ◽  
Author(s):  
Waqar Ahmed ◽  
Pretty S. Philip ◽  
Samir Attoub ◽  
Gulfaraz Khan
Keyword(s):  
Epstein Barr Virus ◽  
Fas Ligand ◽  
Type I ◽  
Dependent Manner ◽  
Extrinsic Pathway ◽  
Barr Virus ◽  
Infected Cells ◽  
Epstein Barr ◽  
Induced Apoptosis ◽  
Cellular Components

Epstein–Barr virus (EBV; human herpesvirus 4) is an oncogenic herpesvirus implicated in the pathogenesis of several human malignancies. A number of recent studies indicate that EBV can manipulate the local microenvironment by excreting viral and cellular components in nanovesicles called exosomes. In this study, we investigated the impact of EBV-derived exosomes on apoptosis of recipient cells and the molecular pathway involved in this process. Exosomes from EBV-infected but not from non-infected cells induced apoptosis in a number of different cell types, including B-cells, T-cells and epithelial cells. However, this phenomenon was not universal and the Burkitt's lymphoma-derived B-cell line BJAB was found to be resistant to apoptosis. Exosomes from both type I and type III EBV latently infected cells induced apoptosis in a dose- and time-dependent manner. Moreover, cells exposed to EBV exosomes did not form colonies in soft agar assays. We further show that fluorescently labelled exosomes derived from EBV-infected cells are taken up by non-infected cells and induce apoptosis via the extrinsic pathway. Inhibition of caspase-3/7/8 blocks EBV exosome-mediated apoptosis. Furthermore, our data indicate that EBV exosomes trigger apoptosis through the Fas ligand (FasL)-mediated extrinsic pathway, as FasL was present in EBV exosomal fractions and anti-FasL antibodies could block EBV exosome-mediated apoptosis. Together, these data support the notion that EBV hijacks the exosome pathway to excrete viral and cellular components that can modulate its microenvironment.

Activation of the small GTPase Cdc42 by the inflammatory cytokines TNF(alpha) and IL-1, and by the Epstein-Barr virus transforming protein LMP1

1999 ◽  
Vol 112 (17) ◽  
pp. 2983-2992 ◽  
Author(s):  
A. Puls ◽  
A.G. Eliopoulos ◽  
C.D. Nobes ◽  
T. Bridges ◽  
L.S. Young ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Epstein Barr Virus ◽  
Actin Polymerization ◽  
Interleukin 1 ◽  
Small Gtpase ◽  
Tnf Alpha ◽  
Nf Kappa B ◽  
Necrosis Factor Alpha ◽  
Barr Virus ◽  
Epstein Barr

Cdc42, a Rho-family GTPase, has been implicated in several signal transduction pathways, including organization of the actin cytoskeleton, activation of the c-Jun N-terminal MAP kinase (JNK) and stimulation of the nuclear transcription factor kappa B (NF(kappa)B). We report here that exposure of fibroblasts to the inflammatory cytokines tumor necrosis factor (alpha) (TNF(alpha)) and interleukin-1 (IL-1) triggers the activation of Cdc42 leading first to filopodia formation and subsequently to Rac and Rho activation. Inhibition of Cdc42 completely suppresses cytokine-induced actin polymerization, but not activation of JNK or NF(kappa)B. The latent membrane protein 1 of Epstein-Barr virus, LMP1, is thought to mimic constitutively activated TNF family receptors. When expressed in fibroblasts, LMP1 stimulates Cdc42-dependent filopodia formation as well as JNK and NF(kappa)B activation. Using LMP1 mutants, we show that activation of Cdc42 and JNK/NF(kappa)B occur through distinct pathways and that Cdc42 activation is independent of LMP1's interaction with TRADD and TRAF proteins.

scholarly journals Enterovirus and herpesviridae family as etiologic agents of lymphomonocytary meningitis, Southern Brazil

2011 ◽  
Vol 69 (3) ◽  
pp. 475-481 ◽  
Author(s):  
Luine Rosele Renaud Vidal ◽  
Sérgio Monteiro de Almeida ◽  
Iara José de Messias-Reason ◽  
Meri Bordignon Nogueira ◽  
Maria do Carmo Debur ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Herpes Virus ◽  
Viral Meningitis ◽  
Etiologic Agent ◽  
Herpes Simplex Virus 1 ◽  
Virus Family ◽  
Barr Virus ◽  
Epstein Barr ◽  
Herpès Virus ◽  
Simplex Virus

Viral meningitis is a common infectious disease of the central nervous system (CNS) that occurs worldwide. The aim of this study was to identify the etiologic agent of lymphomonocytary meningitis in Curitiba, PR, Brazil. During the period of July 2005 to December 2006, 460 cerebrospinal fluid (CSF) samples with lymphomonocytary meningitis were analyzed by PCR methodologies. Fifty nine (12.8%) samples were positive. Enteroviruses was present in 49 (83%) samples and herpes virus family in 10 (17%), of these 6 (10%) herpes simplex virus, 1 (2%) Epstein Barr virus, 2 (3%) human herpes virus type 6 and 1 (2%) mixed infection of enterovirus and Epstein Barr virus. As conclusion enterovirus was the most frequent virus, with circulation during summer and was observed with higher frequency between 4 to 17 years of age. PCR methodology is an important method for rapid detection of RNA enterovirus and DNA herpesvirus in CSF.

scholarly journals Interferon Regulatory Factor 5 Represses Expression of the Epstein-Barr Virus Oncoprotein LMP1: Braking of the IRF7/LMP1 Regulatory Circuit

2005 ◽  
Vol 79 (18) ◽  
pp. 11671-11676 ◽  
Author(s):  
Shunbin Ning ◽  
Leslie E. Huye ◽  
Joseph S. Pagano
Keyword(s):  
Transient Expression ◽  
Epstein Barr Virus ◽  
Interferon Regulatory Factor ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Dependent Manner ◽  
Regulatory Factor ◽  
Barr Virus ◽  
Regulatory Circuit ◽  
Epstein Barr

ABSTRACT We have reported evidence for a positive regulatory circuit between interferon regulatory factor 7 (IRF7) and the Epstein-Barr virus (EBV) oncoprotein 1 (LMP1) (S. Ning, A. M. Hahn, and J. S. Pagano, J. Virol. 77:9359-9368, 2003). To explore a possible braking mechanism for this circuit, several type II EBV-infected cell lines that express different levels of LMP1 and IRF7 proteins and therefore are convenient for studying modulation of expression of LMP1 were analyzed. Endogenous levels of IRF7 and LMP1 were directly correlated. Transient expression of an IRF7 dominant-negative mutant decreased LMP1 levels. Endogenous IRF5 and IRF7 proteins were shown to physically associate in EBV-positive cells. Transient expression of IRF5 decreased activation of the LMP1 promoter by IRF7 in a dose-dependent manner. Finally, transfection of either an IRF5 dominant-negative construct or IRF5 small interfering RNA in these cells resulted in increases in endogenous levels of LMP1. These results indicate that IRF5 can downregulate IRF7's induction of expression of LMP1 most likely by interacting with IRF7 and provide a means of modulating a regulatory circuit between IRF7 and LMP1.

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