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https://www.readbyqxmd.com/read/28644868/electrophysiological-alterations-in-a-murine-model-of-chronic-coxsackievirus-b3-myocarditis
#1
Sven Kaese, Robert Larbig, Matthias Rohrbeck, Gerrit Frommeyer, Dirk Dechering, Jan Olligs, Sabine Schönhofer-Merl, Rainer Wessely, Karin Klingel, Guiscard Seebohm, Lars Eckardt
INTRODUCTION: Coxsackievirus B3 (CVB3) is known to induce acute and chronic myocarditis. Most infections are clinically unapparent but some patients suffer from ventricular arrhythmias (VA) and sudden cardiac death (SCD). Studies showed that acute CVB3 infection may cause impaired function of cardiac ion channels, creating a proarrhythmic substrate. However, it is unknown whether low level CVB3+ expression in myocytes may cause altered cardiac electrophysiology leading to VA. METHODS: Cellular electrophysiology was used to analyze cellular action potentials (APs) and occurrence of afterdepolarizations from isolated cardiomyocytes of wildtype (WT) and transgenic CVB3ΔVP0 (CVB3+) mice...
2017: PloS One
https://www.readbyqxmd.com/read/28642849/aim2-co-immunization-with-vp1-is-associated-with-increased-memory-cd8-t-cells-and-mounts-long-lasting-protection-against-coxsackievirus-b3-challenge
#2
Liang Yin, Dafei Chai, Yan Yue, Chunsheng Dong, Sidong Xiong
The recurrent Coxsackievirus B3 (CVB3) infection is the most important cause of intractable myocarditis which often leads to chronic myocarditis and even dilated cardiomyopathy. Therefore, enhanced DNA vaccines capable of memory CD8 T cells are essential for long-lasting immunological protection against CVB3 infection. In this study, absent in melanoma 2 (AIM2) was used as an adjuvant to enhance the induction of memory CD8 T cells elicited by VP1 (viral capsid protein 1) vaccine. Mice were intramuscularly injected with 50 μg AIM2 plasmid and equal amount of VP1 plasmid (pAIM2/pVP1) vaccine 4 times at 2 week-intervals...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28633417/polypyrimidine-tract-binding-protein-ptb-and-ptb-associated-splicing-factor-in-cvb3-infection-an-itaf-for-an-itaf
#3
Pratik Dave, Biju George, Divya Khandige Sharma, Saumitra Das
The 5΄ UTR of Coxsackievirus B3 (CVB3) contains internal ribosome entry site (IRES), which allows cap-independent translation of the viral RNA and a 5΄-terminal cloverleaf structure that regulates viral replication, translation and stability. Here, we demonstrate that host protein PSF (PTB associated splicing factor) interacts with the cloverleaf RNA as well as the IRES element. PSF was found to be an important IRES trans acting factor (ITAF) for efficient translation of CVB3 RNA. Interestingly, cytoplasmic abundance of PSF protein increased during CVB3 infection and this is regulated by phosphorylation status at two different amino acid positions...
June 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28630939/retrospective-surveillance-of-wastewater-to-examine-seasonal-dynamics-of-enterovirus-infections
#4
Nichole E Brinkman, G Shay Fout, Scott P Keely
Enteroviruses are RNA viruses that are responsible for both mild gastroenteritis and mild respiratory illnesses as well as debilitating diseases such as meningitis and myocarditis. The disease burden of enteroviruses in the United States is difficult to assess because most infections are not recorded. Since infected individuals shed enterovirus in feces and urine, surveillance of municipal wastewater can reveal the diversity of enteroviruses circulating in human populations. Therefore, monthly municipal wastewater samples were collected for 1 year and enteroviruses were quantified by reverse transcriptase quantitative PCR and identified by next-generation, high-throughput sequencing...
May 2017: MSphere
https://www.readbyqxmd.com/read/28560385/the-pi3k-akt-mtor-pathway-is-involved-in-cvb3-induced-autophagy-of-hela-cells
#5
Huan Chang, Xin Li, Qian Cai, Chunyun Li, Lang Tian, Jia Chen, Xiaowei Xing, Yu Gan, Wen Ouyang, Zuocheng Yang
Recent studies have found that viral myocarditis (VMC) associated with coxsackievirus B3 (CVB3) causes autophagy activation after infection, but the specific mechanism is not clear. The present study demonstrated that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB)/mammalian target of rapamycin (mTOR) signaling pathway participates in CVB3‑induced autophagy. We found that the light chain 3 (LC3)‑Ⅱ/LC3‑I ratio was increased and p62 and p‑mTOR were altered at different times during CVB3 infection...
May 31, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28550395/a-critical-role-for-il-21-receptor-signaling-in-the-coxsackievirus-b3-induced-myocarditis
#6
Fan Yang, Xiao-Mou Wei, Wen-Wu Liang, Wen-Hong Mo, Bao-Ping Tan, Hong Wang
To determine whether IL-21 receptor signaling plays a significant role in promoting Tfh cell-mediated cardiac injury in viral myocarditis (VMC), we compared IL-21R-deficient mice for some parameters of VMC. Balb/c and IL-21R(-/-) mice were infected with CVB3. Frequencies of splenic Tfh cells were determined by flow cytometric analysis, and productions of anti-adenine nucleotide translocator (ANT) autoantibodies were detected by enzyme-linked immunosorbent assay. To determine the effects of IL-21R signal on the proliferation of B cells, lymphocytes from spleens of the IL-21R(-/-) and Balb/c mice infected by CVB3 were tagged with carboxyfluorescein succinimidyl ester (CFSE) and then were stimulated with lipopolysaccharides plus IL-21 or anti-IL-21 neutralizing antibody for 3 days...
May 26, 2017: Inflammation
https://www.readbyqxmd.com/read/28539455/functional-consequences-of-rna-5-terminal-deletions-on-coxsackievirus-b3-rna-replication-and-ribonucleoprotein-complex-formation
#7
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
#8
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
#9
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...
June 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28499238/inhibition-of-inos-protects-cardiomyocytes-against-coxsackievirus-b3-induced-cell-injury-by-suppressing-autophagy
#10
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...
July 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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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