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https://www.readbyqxmd.com/read/28539455/functional-consequences-of-rna-5-terminal-deletions-on-coxsackievirus-b3-rna-replication-and-ribonucleoprotein-complex-formation
#1
Nicolas Lévêque, Magali Garcia, Alexis Bouin, Joseph H C Nguyen, Genevieve P Tran, Laurent Andreoletti, Bert L Semler
Group B coxsackieviruses are responsible for chronic cardiac infections. However, the molecular mechanisms by which the virus can persist in the human heart long after the signs of acute myocarditis have abated are still not completely understood. Recently, coxsackievirus B3 strains with 5' terminal deletions in genomic RNAs were isolated from a patient suffering from idiopathic dilated cardiomyopathy, suggesting that such mutant viruses may be the forms responsible for persistent infection. These deletions lacked portions of 5' stem-loop I, which is an RNA secondary structure required for viral RNA replication...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28531186/parvovirus-b19-induced-vascular-damage-in-the-heart-is-associated-with-elevated-circulating-endothelial-microparticles
#2
Katrin Bachelier, Susanne Biehl, Viktoria Schwarz, Ingrid Kindermann, Reinhard Kandolf, Martina Sauter, Christian Ukena, Ali Yilmaz, Karen Sliwa, Claus-Thomas Bock, Karin Klingel, Michael Böhm
BACKGROUND: Diagnosis of viral myocarditis is difficult by clinical criteria but facilitated by detection of inflammation and viral genomes in endomyocardial biopsies. Parvovirus B19 (B19V) targets endothelial cells where viral nucleic acid is exclusively detected in the heart. Microparticles (MPs) are released after cell damage or activation of specific cells. We aimed to investigate whether circulating endothelial MPs (EMPs) in human and experimental models of myocarditis are associated with B19V myocarditis...
2017: PloS One
https://www.readbyqxmd.com/read/28506553/inhibition-of-12-15-lo-ameliorates-cvb3-induced-myocarditis-by-activating-nrf2
#3
Feng Ai, Jiayong Zheng, Yanwei Zhang, Taibing Fan
Cardiac 12/15-lipoxygenase (12/15-LO) was reported to be markedly up-regulated and involved in the development of heart failure. Nuclear factor E2-related factor 2 (Nrf2) plays anti-inflammatory and anti-oxidation roles in response to oxidative stress. However, the role of 12/15-LO in viral myocarditis (VMC) and its underlying molecular mechanism have not yet been elucidated. Here, we demonstrated that 12/15-LO was up-regulated and Nrf2 was down-regulated in coxsackievirus B3 (CVB3)-infected mice and cardiac myocytes...
May 12, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28499238/inhibition-of-inos-protects-cardiomyocytes-against-coxsackievirus-b3-induced-cell-injury-by-suppressing-autophagy
#4
Li Qi, Qi Xin, Jia Wenjun
BACKGROUND: Coxsackievirus B3 (CVB3), a member of the picornavirus family, is one of the major causative enteroviruses of viral myocarditis. The aim of the current study was to investigate the role and underlying mechanism of iNOS and autophagy in CVB3 infected cardiomyocytes. METHODS: Myocardial cell H9c2 were randomly divided into four groups: control group, CVB3 group, CVB3+L-NAME group and the CVB3+iNOS siRNA group. Cell proliferation was detected by MTT method and cell apoptosis was determined by flow cytometric...
May 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28435073/evaluation-of-a-rapid-detection-for-coxsackievirus-b3-using-one-step-reverse-transcription-loop-mediated-isothermal-amplification-rt-lamp
#5
A Monazah, M Zeinoddini, A R Saeeidinia
Coxsackievirus B3 (CVB3) is a member of the genus Enterovirus within the family Picornaviridae and is an important pathogen of viral myocarditis, which accounts for more than 50% viral myocarditis cases. VP1 is major capsid protein that this region has a low homology in both amino acid and nucleotide sequences among Enteroviruses. Therefore we have chosen this region for designed a set of RT-LAMP primers for CVB3 detection. For this the total RNA was extracted from 24-h post infected-HeLa cells with complete cytopathic effect (CPE), and applied to a one-step reverse transcription loop-mediated isothermal amplification reaction (RT-LAMP) using CVB3-specific primers...
April 21, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28381577/understanding-the-mechanism-of-the-broad-spectrum-antiviral-favipiravir-t-705-key-role-of-the-f1-motif-of-the-viral-polymerase
#6
Rana Abdelnabi, Ana Theresa Silveira de Morais, Pieter Leyssen, Isabelle Imbert, Stéphanie Beaucourt, Hervé Blanc, Mathy Froeyen, Marco Vignuzzi, Bruno Canard, Johan Neyts, Leen Delang
Favipiravir (T-705) is a broad-spectrum antiviral agent that has been approved in Japan for treatment of influenza virus infections. T-705 also inhibits the replication of various RNA viruses including chikungunya virus (CHIKV). We demonstrated earlier that the K291R mutation in the F1 motif of the RNA-dependent RNA polymerase (RdRp) of CHIKV is responsible for low-level resistance to T-705. Interestingly, this lysine is highly conserved in the RdRp of positive-sense single-stranded RNA [+ssRNA] viruses. To obtain insights into the unique broad-spectrum antiviral activity of T-705, we explored the role of this lysine using another +ssRNA virus, namely Coxsackievirus B3 (CVB3)...
April 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28359509/autosomal-recessive-cardiomyopathy-presenting-as-acute-myocarditis
#7
Serkan Belkaya, Amy R Kontorovich, Minji Byun, Sonia Mulero-Navarro, Fanny Bajolle, Aurelie Cobat, Rebecca Josowitz, Yuval Itan, Raphaelle Quint, Lazaro Lorenzo, Soraya Boucherit, Cecile Stoven, Sylvie Di Filippo, Laurent Abel, Shen-Ying Zhang, Damien Bonnet, Bruce D Gelb, Jean-Laurent Casanova
BACKGROUND: Myocarditis is inflammation of the heart muscle that can follow various viral infections. Why children only rarely develop life-threatening acute viral myocarditis (AVM), given that the causal viral infections are common, is unknown. Genetic lesions might underlie such susceptibilities. Mouse genetic studies demonstrated that interferon (IFN)-α/β immunity defects increased susceptibility to virus-induced myocarditis. Moreover, variations in human TLR3, a potent inducer of IFNs, were proposed to underlie AVM...
April 4, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28341822/berberine-restricts-coxsackievirus-b-type-3-replication-via-inhibition-of-c-jun-n-terminal-kinase-jnk-and-p38-mapk-activation-in-vitro
#8
Qian Dai, Di Zhang, Hua Yu, Wei Xie, Rong Xin, Lei Wang, Xiaohui Xu, Xiaomei He, Junzhi Xiong, Halei Sheng, Le Zhang, Kebin Zhang, Xiaomei Hu
BACKGROUND At present, the treatment of coxsackievirus-induced myocarditis remains difficult. Berberine (BBR), an isoquinoline alkaloid isolated from traditional medicine herbs, exhibits significant anti-viral efficacy against various viruses. However, the underlying mechanism by which BBR controls CVB3 infection has not yet been reported. The purpose of this study was to investigate the anti-viral efficacy of BBR against CVB3 infection and its mechanism. MATERIAL AND METHODS In our experiments, the protein levels of VP1 and MAPKs signal pathway were measured by Western blot...
March 25, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28278207/pa28-modulates-antigen-processing-and-viral-replication-during-coxsackievirus-b3-infection
#9
Dorota Respondek, Martin Voss, Ina Kühlewindt, Karin Klingel, Elke Krüger, Antje Beling
The function of the proteasome is modulated at the level of subunit expression and by association with its regulatory complexes. During coxsackievirus B3 (CVB3) myocarditis, IFN-induced formation of immunoproteasomes (ip) is known to be critical for regulating immune modulating molecules. The function of the IFN-γ-inducible proteasome regulator subunits PA28 α and β, however, in this context was unknown. During viral myocarditis, we found an increased abundance of PA28β subunits in heart tissue. PA28α/β exists in PA28-20S-PA28 and PA700-20S-PA28 hybrid proteasome complexes in cells both with either predominant ip and standard proteasome (sp) expression...
2017: PloS One
https://www.readbyqxmd.com/read/28264039/in-vivo-t2-weighted-mri-visualizes-cardiac-lesions-in-murine-models-of-acute-and-chronic-viral-myocarditis
#10
Xavier Helluy, Martina Sauter, Yu-Xiang Ye, Gunthard Lykowsky, Jakob Kreutner, Ali Yilmaz, Roland Jahns, Valerie Boivin, Reinhard Kandolf, Peter M Jakob, Karl-Heinz Hiller, Karin Klingel
OBJECTIVE: Acute and chronic forms of myocarditis are mainly induced by virus infections. As a consequence of myocardial damage and inflammation dilated cardiomyopathy and chronic heart failure may develop. The gold standard for the diagnosis of myocarditis is endomyocardial biopsies which are required to determine the etiopathogenesis of cardiac inflammatory processes. However, new non-invasive MRI techniques hold great potential in visualizing cardiac non-ischemic inflammatory lesions at high spatial resolution, which could improve the investigation of the pathophysiology of viral myocarditis...
2017: PloS One
https://www.readbyqxmd.com/read/28247213/microrna-20b-suppresses-the-expression-of-zfp-148-in-viral-myocarditis
#11
Hong-Fei Xu, Xiang-Ting Gao, Jun-Yi Lin, Xue-Hua Xu, Jun Hu, Yu-Jie Ding, Shao-Hua Zhu
Viral myocarditis is a common cardiovascular disease, which seriously endangers the health of people and even leads to sudden unexpected death. MicroRNAs play very important roles in various physical and pathological processes including cardiogenesis and heart diseases. In recent years, miR-20b has been implicated in various diseases such as breast cancer, gastric cancer, hepatocellular carcinoma, cardiovascular diseases. However, the function of miR-20b in the pathological progress of viral myocarditis has not been reported...
May 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28186704/mesenchymal-stromal-cells-modulate-monocytes-trafficking-in-coxsackievirus-b3-induced-myocarditis
#12
Kapka Miteva, Kathleen Pappritz, Muhammad El-Shafeey, Fengquan Dong, Jochen Ringe, Carsten Tschöpe, Sophie Van Linthout
Mesenchymal stromal cell (MSC) application in Coxsackievirus B3 (CVB3)-induced myocarditis reduces myocardial inflammation and fibrosis, exerts prominent extra-cardiac immunomodulation, and improves heart function. Although the abovementioned findings demonstrate the benefit of MSC application, the mechanism of the MSC immunomodulatory effects leading to a final cardioprotective outcome in viral myocarditis remains poorly understood. Monocytes are known to be a trigger of myocardial tissue inflammation. The present study aims at investigating the direct effect of MSC on the mobilization and trafficking of monocytes to the heart in CVB3-induced myocarditis...
April 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28176833/transmissible-endoplasmic-reticulum-stress-from-myocardiocytes-to-macrophages-is-pivotal-for-the-pathogenesis-of-cvb3-induced-viral-myocarditis
#13
Hui Zhang, Yan Yue, Tianle Sun, Xuejie Wu, Sidong Xiong
Infiltrating macrophages have been proven as a pivotal pathological inflammatory cell subset in coxsackievirus B3 (CVB3) induced viral myocarditis. However, the mechanisms underlying the initiation and promotion of macrophage pro-inflammatory responses are still blur. We previously reported that cardiac ER stress contributed to CVB3-induced myocarditis by augmenting inflammation. In this study, we focused on the influence of ER stress on the macrophage inflammatory responses in the viral myocarditis. We found that ER stress was robustly induced in the cardiac infiltrating macrophages from CVB3-infected mice, and robustly facilitated the production of pro-inflammatory cytokines (IL-6, IL-12, MCP-1 and IP-10)...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174228/profiling-subcellular-protein-phosphatase-responses-to-coxsackievirus-b3-infection-of-cardiomyocytes
#14
Millie Shah, Christian M Smolko, Sarah Kinicki, Zachary D Chapman, David L Brautigan, Kevin A Janes
Cellular responses to stimuli involve dynamic and localized changes in protein kinases and phosphatases. Here, we report a generalized functional assay for high-throughput profiling of multiple protein phosphatases with subcellular resolution and apply it to analyze coxsackievirus B3 (CVB3) infection counteracted by interferon signaling. Using on-plate cell fractionation optimized for adherent cells, we isolate protein extracts containing active endogenous phosphatases from cell membranes, the cytoplasm, and the nucleus...
April 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28148910/intein-mediated-backbone-cyclization-of-vp1-protein-enhanced-protection-of-cvb3-induced-viral-myocarditis
#15
Xingmei Qi, Sidong Xiong
CVB3 is a common human pathogen to be highly lethal to newborns and causes viral myocarditis and pancreatitis in adults. However, there is no vaccine available for clinical use. CVB3 capsid protein VP1 is an immunodominant structural protein, containing several B- and T-cell epitopes. However, immunization of mice with VP1 protein is ineffective. Cyclization of peptide is commonly used to improve their in vivo stability and biological activity. Here, we designed and synthesizd cyclic VP1 protein by using engineered split Rma DnaB intein and the cyclization efficiency was 100% in E...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28137624/incorporation-of-a-bi-functional-protein-fimh-enhances-the-immunoprotection-of-chitosan-pvp1-vaccine-against-coxsackievirus-b3-induced-myocarditis
#16
Xiangmei Fan, Yan Yue, Sidong Xiong
Viral myocarditis is a common clinical cardiovascular disease mainly induced by coxsackievirus B3 (CVB3) with no effective therapeutic measures. Induction of efficient mucosal immune responses is very critical against CVB3-induced myocarditis. FimH is an Escherichia coli (E. coli)-derived protein, which possesses an M cell-targeting property and functions as a TLR4 agonist. In this study, we introduced the recombinant FimH protein, into our previously developed CVB3 mucosal vaccine chitosan (CS)-pVP1, aiming to provoke more efficient mucosal immune responses and immunoprotection against CVB3-induced myocarditis...
April 2017: Antiviral Research
https://www.readbyqxmd.com/read/28131843/inhibition-of-drp1-attenuates-mitochondrial-damage-and-myocardial-injury-in-coxsackievirus-b3-induced-myocarditis
#17
Lin Lin, Ming Zhang, Rui Yan, Hu Shan, Jiayu Diao, Jin Wei
Viral myocarditis (VMC) is closely related to apoptosis, oxidative stress, innate immunity, and energy metabolism, which are all linked to mitochondrial dysfunction. A close nexus between mitochondrial dynamics and cardiovascular disease with mitochondrial dysfunction has been deeply researched, but there is still no relevant report in viral myocarditis. In this study, we aimed to explore the role of Dynamin-related protein 1 (Drp1)-linked mitochondrial fission in VMC. Mice were inoculated with the Coxsackievirus B3 (CVB3) and treated with mdivi1 (a Drp1 inhibitor)...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28129450/viral-encephalitis-after-haplo-identical-hematopoietic-stem-cell-transplantation-causative-viral-spectrum-characteristics-and-risk-factors
#18
Xiao-Hui Zhang, Jia-Min Zhang, Wei Han, Huan Chen, Yu-Hong Chen, Feng-Rong Wang, Jing-Zhi Wang, Yuan-Yuan Zhang, Xiao-Dong Mo, Yao Chen, Yu Wang, Ying-Jun Chang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang
OBJECTIVE: To retrospectively identify characteristics and risk factors of viral encephalitis (VE) in patients who underwent a haplo-identical hematopoietic stem cell transplant (HSCT). METHODS: A nested case-control study was designed. Cases with VE and controls were identified from a cohort composed of 1274 patients who underwent a haplo-identical HSCT from 2012 to 2015. RESULTS: VE was identified in 30 patients (2.4%). The median time from HSCT to diagnosis was 144...
January 27, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28123495/effects-of-the-mapk-pathway-and-the-expression-of-car-in-a-murine-model-of-viral-myocarditis
#19
Ling Niu, Chunli Li, Zhenzhou Wang, Hui Xu, Xinjiang An
The pathogenesis of viral myocarditis (VMC) is not fully understood. This study aimed to examine the relationship between coxsackie-adenovirus receptor (CAR) and the p38 mitogen activated protein kinase (MAPK) pathway mechanisms in a mouse model. Three groups of mice were established: 5 mice in a control group injected with saline, 15 in the model group injected with coxsackie virus B3 (CVB) and 15 in the intervention group injected with CVB3 but treated with the p38 MAPK inhibitor SB203580. Mice were sacrificed at days 1, 5, 10, 15 and 30 and cardiac tissues were isolated to perform the tests...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28110209/expansion-of-cd11b-ly-6c-myeloid-derived-suppressor-cells-mdscs-driven-by-galectin-9-attenuates-cvb3-induced-myocarditis
#20
Yingying Zhang, Mengying Zhang, Xueqin Li, Zongsheng Tang, Ling He, Kun Lv
Galectin-9 is known to play a role in the modulation of innate and adaptive immunity to ameliorate CVB3-induced myocarditis. In the present study, we found that galectin-9 induced the expansion of CD11b(+)Ly-6C(+) myeloid-derived suppressor cells (MDSCs) in the heart from CVB3-infected mice. Adoptive transfer of CD11b(+)Ly-6C(+) MDSCs significantly alleviated myocarditis accompanied by increased Th2 and Treg frequency and anti-inflammatory cytokines expression in the heart tissue. Moreover, Ly6C(+) MDSCs, but not Ly6G(+) cells, expressed Arg-1 and NOS2, and suppressed CD4(+) T cell proliferation in vitro in an Arg-1-dependent mechanism; an event that was reversed with treatment of either an Arg-1 inhibitor or addition of excess l-arginine...
March 2017: Molecular Immunology
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