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https://www.readbyqxmd.com/read/29108785/semaphorin7a-aggravates-coxsackievirusb3-induced-viral-myocarditis-by-increasing-%C3%AE-1%C3%AE-1-integrin-macrophages-and-subsequent-enhanced-inflammatory-response
#1
Xuejie Wu, Yawen Meng, Chao Wang, Yan Yue, Chunsheng Dong, Sidong Xiong
Semaphorin7A (Sema7A) has been reported to play various roles in nerve axon growth, tumor suppression, and tissue remodeling, as well as regulation of intestinal inflammation diseases. Viral myocarditis (VMC) characterized by viral-myocardial-cell necrosis and inflammatory cell infiltration is a common clinical disease of the cardiovascular system. However, the role of Sema7A in coxsackievirus B3 (CVB3)-induced VMC has not been reported. In this study, we generated an acute VMC mouse model by CVB3 infection, and manipulated Sema7A expression by in vivo polyethyleneimine-mediated Sema7A down-regulation...
November 3, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29096746/overexpression-of-microrna-133b-reduces-myocardial-injuries-in-children-with-viral-myocarditis-by-targeting-rab27b-gene
#2
Y Zhang, L Sun, H Sun, X Liu, X Luo, C Li, D Sun, T Li
The present study is to measure the expression of microRNA (miRNA or miR)-133b in circulating blood of children with viral myocarditis before and after drug treatment, and to investigate its relationship with the severity of myocardial lesions. A total of 36 children patients with viral myocarditis who received treatments at our hospital between June 2014 and June 2016 were enrolled in the present study, including 21 boys and 15 girls (age range, 9 months - 16 years).Quantitative real-time polymerase chain reaction was used to determine the expression of miR-133b in peripheral blood of patients and cardiomyocytes infected with CVB3...
October 31, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/29043768/infection-of-ipsc-lines-with-miscarriage-associated-coxsackievirus-and-measles-virus-and-teratogenic-rubella-virus-as-a-model-for-viral-impairment-of-early-human-embryogenesis
#3
Denise Hübner, Kristin Jahn, Sandra Pinkert, Janik Böhnke, Matthias Jung, Henry Fechner, Dan Rujescu, Uwe Gerd Liebert, Claudia Claus
Human induced pluripotent stem cell (iPSC) lines are a promising model for the early phase of human embryonic development. Here, their contribution to the still incompletely understood pathogenesis of congenital virus infections was evaluated. The infection of iPSC lines with miscarriage-associated coxsackievirus B3 (CVB3) and measles virus (MV) was compared to the efficient teratogen rubella virus (RV). While CVB3 and MV were found to be cytopathogenic on iPSC lines, RV replicated without impairment of iPSC colony morphology and integrity...
October 26, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29043433/mcpip1-inhibits-coxsackievirus-b3-replication-by-targeting-viral-rna-and-negatively-regulates-virus-induced-inflammation
#4
Min Li, Kepeng Yan, Lin Wei, Yang Yang, Qian Qian, Wei Xu
Monocyte chemotactic protein-induced protein 1(MCPIP1) is identified as an important inflammatory regulator during immune response. MCPIP1 possesses antiviral activities against several viruses, such as Japanese encephalitis. However, its role on Coxsackievirus B3 (CVB3) infection, a positive-stranded RNA virus, has not been addressed. Here, we reported that MCPIP1 was up-regulated in cardiomyocytes by CVB3 infection and in hearts and pancreas of infected mice. Then we found that overexpression of MCPIP1 inhibited CVB3 replication and knockdown of it promoted virus replication...
October 17, 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/29039143/cd80-regulates-th17-cell-differentiation-in-coxsackie-virus-b3-induced-acute-myocarditis
#5
Yanlan Huang, Yong Li, Bin Wei, Weifeng Wu, Xingcui Gao
The cluster of differentiation protein complex, CD80/CD86, regulates Th1/Th2 differentiation in autoimmune disease. In order to establish the effects of CD80/CD86 on Th17 cell differentiation in acute viral myocarditis (VMC), we infected C57BL/6 mice with Coxsackie virus B3 (CVB3) and examined the effects of the treatment with anti-CD80/CD86 monoclonal antibodies (mAbs) on Th17 cell differentiation in vivo. The effects of anti-CD80/CD86 mAbs on Th17 cell differentiation were further evaluated in vitro. The treatment with anti-CD80 mAb induced marked suppression of Th17 cell differentiation and ROR-γt mRNA expression, whereas anti-CD86 mAb alone had no effect, both in vivo and in vitro...
October 16, 2017: Inflammation
https://www.readbyqxmd.com/read/29036974/-the-impact-of-hydrogen-sulfide-on-the-heme-oxygenase-1-carbon-monoxide-system-in-coxsackie-virus-b3-induced-myocarditis-in-mice
#6
S Y Zhang, T T Wu, Y Ren, T H Xia, R Z Wu
Objective: To explore the impact of hydrogen sulfide (H(2)S) on the heme oxygenase-1/carbon monoxide pathway in Coxsackie virus B3 (CVB3)-induced murine myocarditis (VMC) model. Method: A total of 70 inbred male Balb/c mouse (4-6 weeks old) were randomized into the following four groups: Normal, VMC, PAG and NaHS (n=10 for Normal, n=20 for VMC, PAG and NaHS groups). Mice in Normal group were non-infected mice treated with intraperitoneal injection of sterile phosphate-buffered saline daily for 10 days.Mice in VMC group received intraperitoneal CVB3 injection (0...
September 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/29032641/cholic-acid-attenuate-er-stress-induced-cell-death-in-coxsackievirus-b3-infection
#7
Jae-Young Han, Hae In Jeong, Cheol-Woo Park, Jisoo Yoon, Jaeyoung Ko, Sang-Jip Nam, Byung-Kwan Lim
Coxsackievirus Type B3 (CVB3) is an enterovirus that belongs to the Picornaviridae and causes of various diseases such as myocarditis and hand-foot-mouth diseases. But effective antiviral drug was still not developed. In this study, we looking for potential inhibitors of CVB3 replication by examining survival of CVB3-infected HeLa cells. We detected an antiviral effect of cholic acid and identified it as a candidate inhibitor of CVB3 replication. Cholic acid circulates in the liver and intestines, and it helps digestion and absorption of lipids in small intestine...
October 14, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29024767/modulation-of-proteolytic-polyprotein-processing-by-coxsackievirus-mutants-resistant-to-inhibitors-targeting-phosphatidylinositol-4-kinase-iii%C3%AE-or-oxysterol-binding-protein
#8
Heyrhyoung Lyoo, Cristina M Dorobantu, Hilde M van der Schaar, Frank J M van Kuppeveld
Enteroviruses (e.g. poliovirus, coxsackievirus, and rhinovirus) require several host factors for genome replication. Among these host factors are phosphatidylinositol-4-kinase IIIβ (PI4KB) and oxysterol binding protein (OSBP). Enterovirus mutants resistant to inhibitors of PI4KB and OSBP were previously isolated, which demonstrated a role of single substitutions in the non-structural 3A protein in conferring resistance. Besides the 3A substitutions (i.e., 3A-I54F and 3A-H57Y) in coxsackievirus B3 (CVB3), substitution N2D in 2C was identified in each of the PI4KB-inhibitor resistant CVB3 pools, but its possible benefit has not been investigated yet...
October 9, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28993161/new-class-of-early-stage-enterovirus-inhibitors-with-a-novel-mechanism-of-action
#9
Yipeng Ma, Rana Abdelnabi, Leen Delang, Mathy Froeyen, Walter Luyten, Johan Neyts, Carmen Mirabelli
4-dimethylamino benzoic acid (compound 12, synonym: 4EDMAB) was identified as an in vitro inhibitor of Coxsackie virus B3 (CVB3) replication in CPE-based assays (EC50 of 9.1 ± 1.5 μM). Next, the activity of twenty-three analogues was assessed, their structure-activity relationship was deduced and a more potent analogue was identified (EC50 of 2.6 ± 0.5 μM). The antiviral activity of 4EDMAB was further confirmed by quantifying viral RNA yield. Time-of-drug-addition assay revealed that 4EDMAB exerts its antiviral activity at the early stages of virus replication...
October 7, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28986246/sphingosine-1-phosphate-alleviates-coxsackievirus-b3-induced-myocarditis-by-increasing-invariant-natural-killer-t-cells
#10
Xinggang Wang, Yong Yu, Minghui Li, Ying Yu, Guijian Liu, Yeqing Xie, Yuxi Liu, Xiangdong Yang, Yunzeng Zou, Junbo Ge, Ruizhen Chen
Sphingosine 1-phosphate (S1P), via binding to its specific receptors of S1PR1, participates in the regulation of both innate and adaptive immunity. Recent reports have identified S1P as a messenger mediating inflammation. However, roles of S1P in Coxsackievirus B3 (CVB3)-induced myocarditis were largely unknown. Here, we investigated the effect of S1P treatment on CVB3-induced myocarditis in vivo. We found that CVB3 infection downregulated S1PR1 expression in spleen and decreased the proportion of invariant natural killer T cells (iNKT) in CD3 positive T cells both in spleen and in blood from left ventricle, which accompanied by severe inflammation lesions and more virus capsid protein (VP1) expression in heart tissue...
October 3, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28983639/ginsenoside-rb3-inhibits-endothelial-mesenchymal-transition-of-cardiac-microvascular-endothelial-cells
#11
L Yang, Q Liu, Y Yu, H Xu, S Chen, S Shi
BACKGROUND: We investigated the effect of Ginsenoside-Rb3 (Rb3) on the endothelial-to-mesenchymal transition (EMT) of cardiac microvascular endothelial cells (CMVECs) following coxsackievirus B3 (CVB3) infection. METHODS: CMVECs were infected with 100 TCID50 CVB3 (CVB3 group) or treated with Rb3 (Rb3 group); stably cultured CMVECs were used as control. Cells treated with the Pyk2 inhibitor TAE226 and PI3K inhibitor LY294002 were used for additional experiments. Cell viability was assessed with the Cell Counting Kit-8 (CCK8)...
October 5, 2017: Herz
https://www.readbyqxmd.com/read/28973047/tlr3-is-required-for-survival-following-coxsackievirus-b3-infection-by-driving-t-lymphocyte-activation-and-polarization-the-role-of-dendritic-cells
#12
Renata Sesti-Costa, Marcela Cristina Santiago Françozo, Grace Kelly Silva, José Luiz Proenca-Modena, João Santana Silva
Type B coxsackievirus (CVB) is a common cause of acute and chronic myocarditis, meningitis and pancreatitis, often leading to heart failure and pancreatic deficiency. The polarization of CD4+ T lymphocytes and their cytokine milieu are key factors in the outcome of CVB-induced diseases. Thus, sensing the virus and driving the adaptive immune response are essential for the establishment of a protective immune response. TLR3 is a crucial virus recognition receptor that confers the host with resistance to CVB infection...
2017: PloS One
https://www.readbyqxmd.com/read/28950225/immunological-and-pathological-consequences-of-coxsackievirus-rna-persistence-in-the-heart
#13
Claudia T Flynn, Taishi Kimura, Kwesi Frimpong-Boateng, Stephanie Harkins, J Lindsay Whitton
Type B coxsackieviruses (CVB) can cause myocarditis and dilated cardiomyopathy (DCM), a potentially-fatal sequela that has been correlated to the persistence of viral RNA. Herein, we demonstrate that cardiac RNA persistence can be established even after an inapparent primary infection. Using an inducible Cre/lox mouse model, we ask: (i) Does persistent CVB3 RNA cause ongoing immune activation? (ii) If T1IFN signaling into cardiomyocytes is ablated after RNA persistence is established, is there any change in the abundance of persistent CVB3 RNA and/or does cytopathic infectious virus re-emerge? (iii) Does this loss of T1IFN responsiveness by cardiomyocytes lead to the recurrence/exacerbation of myocarditis? Our findings suggest that persistent enteroviral RNAs probably do not contribute to ongoing myocardial disease, and are more likely to be the fading remnants of a recent, possibly sub-clinical, primary infection which may have set in motion the process that ultimately ends in DCM...
December 2017: Virology
https://www.readbyqxmd.com/read/28944873/coxsackieviruses-b3-infection-of-myocardial-microvascular-endothelial-cells-activates-fractalkine-via-the-erk1-2-signaling-pathway
#14
Jili Wen, Congxin Huang
Infections by pathogens may lead to cardiovascular diseases, including acute/chronic myocarditis. (Coxsackieviruses B3) CVB3 is considered to be the most common causative agent in m‑yocarditis, which can lead to dilated cardiomyopathy. The present study aimed to investigate the mechanism of CVB3‑infected myocardial microvascular endothelial cells. The CVB3 infection was detected by 50% tissue culture infective dose (TCID50). The role of fractalkine (FKN) in the infection was detected using western blotting and RNA interference...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28922636/effects-of-mutations-on-active-site-conformation-and-dynamics-of-rna-dependent-rna-polymerase-from-coxsackievirus-b3
#15
Hujun Shen, Mingsen Deng, Yachao Zhang
Recent crystal structures of RNA-dependent RNA polymerase (3D(pol)) from Coxsackievirus B3 (CVB3) revealed that a tyrosine mutation at Phe364 (F364Y) resulted in structures with open active site whereas a hydrophobic mutation at Phe364 (F364A) led to conformations with closed active site. Besides, the crystal structures showed that the F364W mutation had no preference between the open and closed active sites, similar to wild-type. In this paper, we present a molecular dynamics (MD) study on CVB3 3D(pol) in order to address some important questions raised by experiments...
September 12, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28914420/labdane-type-diterpenoids-from-vitex-limonifolia-and-their-antivirus-activities
#16
Ninh Khac Ban, Nguyen Thi Kim Thoa, Tran My Linh, Do Thi Trang, Phan Van Kiem, Nguyen Xuan Nhiem, Bui Huu Tai, Chau Van Minh, Jae-Hyoung Song, Hyun-Jeong Ko, Seung Hyun Kim
Phytochemical investigation of the methanol extract of Vitex limonifolia leaves led to the isolation of three new labdane-type diterpenoids, vitexlimolides A-C (1-3) and eight known compounds, 5,4'-dihydroxy-3,7-dimethoxyflavone (4), vitecetin (5), 5,4'-dihydroxy-7,3'-dimethoxyflavone (6), verrucosin (7), 2α, 3α-dihydroxy-urs-12-en-28-oic acid (8), euscaphlic acid (9), 18,19-seco, 2α, 3α-dihydroxy-19-oxo-urs-11,13(18)-dien-28-oic acid (10), and maslinic acid (11). Their chemical structures were elucidated by physical and chemical methods...
September 15, 2017: Journal of Natural Medicines
https://www.readbyqxmd.com/read/28912259/nod2-nucleotide-binding-oligomerization-domain-2-is-a-major-pathogenic-mediator-of-coxsackievirus-b3-induced-myocarditis
#17
Carsten Tschöpe, Irene Müller, Yu Xia, Konstantinos Savvatis, Kathleen Pappritz, Sandra Pinkert, Dirk Lassner, Markus M Heimesaat, Frank Spillmann, Kapka Miteva, Stefan Bereswill, Heinz-Peter Schultheiss, Henry Fechner, Burkert Pieske, Uwe Kühl, Sophie Van Linthout
BACKGROUND: The cytoplasmatic pattern recognition receptor, NOD2 (nucleotide-binding oligomerization domain 2), belongs to the innate immune system and is among others responsible for the recognition of single-stranded RNA. With Coxsackievirus B3 (CVB3) being a single-stranded RNA virus, and the recent evidence that the NOD2 target, NLRP3 (NOD-like receptor family, pyrin domain containing 3) is of importance in the pathogenesis of CVB3-induced myocarditis, we aimed to unravel the role of NOD2 in CVB3-induced myocarditis...
September 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28887702/necroptosis-may-be-a-novel-mechanism-for-cardiomyocyte-death-in-acute-myocarditis
#18
Fei Zhou, Xuejun Jiang, Lin Teng, Jun Yang, Jiawang Ding, Chao He
In this study, we investigated the roles of RIP1/RIP3 mediated cardiomyocyte necroptosis in CVB3-induced acute myocarditis. Serum concentrations of creatinine kinase (CK), CK-MB, and cardiac troponin I were detected using a Hitachi Automatic Biochemical Analyzer in a mouse model of acute VMC. Histological changes in cardiac tissue were observed by light microscope and expression levels of RIP1/RIP3 in the cardiac tissue were detected via Western blot and immunohistochemistry. The data showed that RIP1/RIP3 was highly expressed in cardiomyocytes in the acute VMC mouse model and that the necroptosis pathway specific blocker, Nec-1, dramatically reduced the myocardial damage by downregulating the expression of RIP1/RIP3...
September 8, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28886971/traf6-a-player-in-cvb3-induced-myocarditis
#19
Oana N Ursu, Tina Beyer, Martina Sauter, Annunziata Fragasso, Sandra Bundschuh, Karin Klingel, Barbara Munz
Coxsackievirus B3 (CVB3) is an important inducer of myocarditis, which, in susceptible individuals, can chronify and eventually lead to the development of dilated cardiomyopathy and heart failure. The respective mechanisms are not completely understood. Here, we analyzed expression of the TRAF6 gene, encoding TNF receptor-associated factor 6 (TRAF6), a signal transduction scaffold protein that acts downstream of cytokine receptors, in heart tissue of susceptible and non-susceptible mouse strains. We found that after infection, TRAF6 expression was upregulated in both non-susceptible C57BL/6 wildtype and susceptible A...
September 5, 2017: Cytokine
https://www.readbyqxmd.com/read/28883283/oncolytic-coxsackievirus-therapy-as-an-immunostimulator
#20
Shohei Miyamoto, Miyako Sagara, Hiroshi Kohara, Kenzaburo Tani
Recently, the active development of oncolytic virotherapy has gathered attention. Enterovirus research seeks to better understand its pathogenicity. In particular, coxsackievirus A21 (CVA21) is a promising candidate for oncolytic virotherapy, and thus is the focus of many clinical trials. We have reported that coxsackievirus B3 (CVB3) had potent oncolytic activity for cancer, and induced immunogenic cell death of CVB3-infected cells. We then genetically engineered wild type CVB3 and successfully produced a novel recombinant CVB3-miRT, improving its safety by the introducing an organ-specific miRNA target sequence...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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