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Michelle P Ashton, Anne Eugster, Denise Walther, Natalie Daehling, Stephanie Riethausen, Denise Kuehn, Karin Klingel, Andreas Beyerlein, Stephanie Zillmer, Anette-Gabriele Ziegler, Ezio Bonifacio
Viral infections are associated with autoimmunity in type 1 diabetes. Here, we asked whether this association could be explained by variations in host immune response to a putative type 1 etiological factor, namely coxsackie B viruses (CVB). Heterogeneous antibody responses were observed against CVB capsid proteins. Heterogeneity was largely defined by different binding to VP1 or VP2. Antibody responses that were anti-VP2 competent but anti-VP1 deficient were unable to neutralize CVB, and were characteristic of children who developed early insulin-targeting autoimmunity, suggesting an impaired ability to clear CVB in early childhood...
2016: Scientific Reports
Rashad Al-Salahi, Hatem A Abuelizz, Hazem A Ghabbour, Rabab El-Dib, Mohamed Marzouk
BACKGROUND: The persistent appearance of viral strains that causes a resistant viral infection has led to continuous trials for the design and development of novel antiviral compounds. Benzoquinazoline compounds have been reported to exhibit an interesting antiviral activity. This work aims to study and evaluate the antiviral activity of a newly prepared 2-thioxo-benzo[g]quinazolin-4(3H)-one series against herpes simplex (HSV-1 & 2) and coxsackievirus (CVB4). METHODS: The antiviral activity was performed using the MTT assay, in which Vero cells (obtained from the American Type Culture Collection, ATCC) were propagated in fresh Dulbecco's Modified Eagle's Medium (DMEM) and challenged with 10(4) doses of the virus...
2016: Chemistry Central Journal
Xin Han, Ningyuan Sun, Haoming Wu, Deyin Guo, Po Tien, Chune Dong, Shuwen Wu, Hai-Bing Zhou
Enterovirus 71 (EV71) plays an important role in hand-foot-and-mouth disease. In this study, a series of diarylhydrazide analogues was synthesized, and the systematic exploration of SAR led to potent enterovirus inhibitors, of which compound 15 exhibits significant improvements in inhibition potency with an EC50 value of 0.02 μM against EV71. It is very interesting that this class of diarylhydrazides exhibits activities against a series of human enteroviruses at the picomolar level, including EV71 and Coxsackieviruses B1 (CVB1), CVB2, CVB3, CVB4, CVB5, and CVB6 (EC50 as low as 0...
March 10, 2016: Journal of Medicinal Chemistry
Anastasia V Galochkina, Vadim B Anikin, Vasily A Babkin, Liudmila A Ostrouhova, Vladimir V Zarubaev
Members of the family Picornaviridae, in particular, enteroviruses, represent a serious threat to human health. They are responsible for numerous pathologies ranging from mild disease to fatal outcome. Due to the limited number of safe and effective antivirals against enteroviruses, there is a need for search and development of novel drugs with various mechanisms of activity against enteroviruses-induced pathologies. We studied the effect of dihydroquercetin (DHQ), a flavonoid from larch wood, on the course of pancreatitis of white mice caused by coxsackievirus B4 (CVB4)...
April 2016: Archives of Virology
Enagnon Kazali Alidjinou, Famara Sané, Jacques Trauet, Marie-Christine Copin, Didier Hober
Beyond acute infections, group B coxsackieviruses (CVB) are also reported to play a role in the development of chronic diseases, like type 1 diabetes. The viral pathogenesis mainly relies on the interplay between the viruses and innate immune response in genetically-susceptible individuals. We investigated the interaction between CVB4 and macrophages considered as major players in immune response. Monocyte-derived macrophages (MDM) generated with either M-CSF or GM-CSF were inoculated with CVB4, and infection, inflammation, viral replication and persistence were assessed...
November 2015: Viruses
Natalia F Lomakina, Elena Yu Shustova, Olga M Strizhakova, Jan Felix Drexler, Alexander N Lukashev
Swine vesicular disease virus (SVDV) emerged around 1960 from a human enterovirus ancestor, coxsackievirus B5 (CVB5), and caused a series of epizootics in Europe and Asia. We characterized a coxsackievirus B4 strain that caused an epizootic involving 24 488 pigs in the Soviet Union in 1975. Phylogenetic evidence suggested that the swine virus emerged from a human ancestor between 1945 and 1975, almost simultaneously with the transfer of CVB5.
January 2016: Journal of General Virology
Martina Aumayr, Sofiya Fedosyuk, Katharina Ruzicska, Carla Sousa-Blin, Georg Kontaxis, Tim Skern
Messenger RNA is recruited to the eukaryotic ribosome by a complex including the eukaryotic initiation factor (eIF) 4E (the cap-binding protein), the scaffold protein eIF4G and the RNA helicase eIF4A. To shut-off host-cell protein synthesis, eIF4G is cleaved during picornaviral infection by a virally encoded proteinase; the structural basis of this reaction and its stimulation by eIF4E is unclear. We have structurally and biochemically investigated the interaction of purified foot-and-mouth disease virus (FMDV) leader proteinase (Lb(pro)), human rhinovirus 2 (HRV2) 2A proteinase (2A(pro)) and coxsackievirus B4 (CVB4) 2A(pro) with purified eIF4GII, eIF4E and the eIF4GII/eIF4E complex...
December 2015: Protein Science: a Publication of the Protein Society
Enagnon Kazali Alidjinou, Wassim Chehadeh, Jacques Weill, Marie-Christine Vantyghem, Chantal Stuckens, Anne Decoster, Christine Hober, Didier Hober
BACKGROUND: Intracellular enterovirus (EV) RNA was detected in blood of patients with type 1 diabetes (T1D). The presence of EV RNA in subsets of peripheral blood mononuclear cells (PBMCs) of patients, and the in vitro infection of these cells with an EV, was investigated. MATERIALS AND METHODS: Blood was collected from 42 patients with T1D, PBMCs were isolated and monocytes were purified. Interferon alpha (IFNα) mRNA and EV RNA were investigated using RT-PCR. Levels of IFNα in plasma were measured using an immunoassay...
September 2015: European Journal of Clinical Investigation
Chia-Feng Yeh, Kuo-Chih Wang, Chi-Yu Lu, Lien-Chai Chiang, Den-En Shieh, Ming-Hong Yen, Jung-San Chang
Enterovirus 71 (EV71) can cause central nervous system infections with mortality and neurologic sequelae. At present, there is no effective therapeutic modality for EV71 infection. The infection is more common in families with poor socioeconomic status. Therefore, finding a readily available, cost-effective therapeutic modality would be very helpful to these socioeconomically disadvantaged families. Yakammaoto is a cheap and readily available traditional prescription that is proven to have antiviral activity against coxsackievirus B4 (CVB4)...
June 2015: Kaohsiung Journal of Medical Sciences
Diana Rodà, Esther Pérez-Martínez, María Cabrerizo, Gloria Trallero, Aina Martínez-Planas, Carles Luaces, Juan-José García-García, Carmen Muñoz-Almagro, Cristian Launes
UNLABELLED: Enterovirus (EV) infection is common in infants, but the information with regard to the molecular epidemiology and the associations between types and clinical variables is very scarce. This study includes 195 children <3 months old with fever, attended from March 2010 to December 2012 in an emergency department of a tertiary paediatric hospital in whom EV infection was confirmed by real-time PCR in blood and/or cerebrospinal fluid. Clinical and epidemiological data was prospectively collected...
November 2015: European Journal of Pediatrics
Juying Yan, Ziping Miao, Huakun Lyu, Jiayue Zhou, Liming Gong, Haiyan Mao, Yi Sun, Yanjun Zhang
OBJECTIVE: To investigate pathogens and molecular-epidemiology characteristics of viral meningoencephalitis in the monitoring sites of Zhejiang province, 2013. METHODS: Cerebrospinal fluid and/or stool specimens were collected from suspected patients admitted to the monitoring hospitals in southern and northern Zhejiang province. Such specimen were subject to real-time qPCR for the detection of Human enterovirus (HEV), Japanese encephalitis virus (JEV), Mumps virus (MuV), Herpes simplex virus (HSV) and Cytomegalovirus (CMV)...
March 2015: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
Swan Firquet, Sophie Beaujard, Pierre-Emmanuel Lobert, Famara Sané, Delphine Caloone, Daniel Izard, Didier Hober
In the present study, we evaluated the viability of non-enveloped viruses, minute virus of mice (MVM) and coxsackievirus B4 (CVB4), and enveloped-viruses, influenza A virus (H1N1) and herpes simplex virus type 1 (HSV-1), on surfaces. We also investigated the impact of the initial concentration of proteins and sodium chloride on the persistence of infectious CVB4 on surfaces. Viral suspensions (>10(4.5) TCID50) were applied to petri dish lids and dried under the air flow of a biosafety cabinet. The recovered viral preparations were titered on appropriate cell lines...
2015: Microbes and Environments
Yanju Zhu, Yue Pan, Junying Chen, Jiansheng Liu, Wei Chen, Shaohui Ma
Coxsackievirus B4 is a member of the species Enterovirus B in the Enterovirus genus of the Picornaviridae family. So far, there are only seven complete genome sequences of CVB4 published in GenBank database. In the study, the complete genome analysis of a Coxsackievirus B4 strain A155/YN/CHN/2009 isolated from a child with aseptic meningitis in Yunnan Province was performed. It had 85.1 and 83.3 % nucleotide similarity with prototype strain J.V.B Benschoten in the VP1 region and the complete genome, respectively...
June 2015: Virus Genes
Enagnon Kazali Alidjinou, Famara Sané, Antoine Bertin, Delphine Caloone, Didier Hober
Group B Coxsackieviruses (CVB) are involved in various acute clinical features and they can play a role in the development of chronic diseases like type 1 diabetes. The persistence of CVB has been described in vitro and in vivo in various models. Fluoxetine was reported to inhibit the replication of CVB1-3, which prompted us to study the in vitro antiviral activity of fluoxetine against CVB4 in models of acute infection. In addition we took advantage of a chronically CVB4-infected Panc-1 cell line to evaluate the antiviral effect of fluoxetine in a model of persistent CVB4 infection...
April 2015: Antiviral Research
Swan Firquet, Sophie Beaujard, Pierre-Emmanuel Lobert, Famara Sané, Delphine Caloone, Daniel Izard, Didier Hober
Heat inactivation of viruses was reported, however, the thermal resistance of viruses in droplets has not been studied. The aim of this study was to evaluate the pattern of heat resistance of minute virus of mice (MVM), coxsackievirus B4 (CVB4), influenza A virus (H1N1), and herpes simplex virus type 1 (HSV1) contained in droplets. Four μL droplets containing viruses (> 10(4.5) TCID50) were applied onto warmed surface obtained by using a self-made heating device. Viral suspensions were exposed to temperatures ranging from 70 to 130°C for 0 to 90 min depending on the virus, and then the recovered viral preparations were tittered...
2014: Microbes and Environments
Kelly D McCall, Jean R Thuma, Maria C Courreges, Fabian Benencia, Calvin B L James, Ramiro Malgor, Noriko Kantake, William Mudd, Nathan Denlinger, Bret Nolan, Li Wen, Frank L Schwartz
Group B coxsackieviruses (CVBs) are involved in triggering some cases of type 1 diabetes mellitus (T1DM). However, the molecular mechanism(s) responsible for this remain elusive. Toll-like receptor 3 (TLR3), a receptor that recognizes viral double-stranded RNA, is hypothesized to play a role in virus-induced T1DM, although this hypothesis is yet to be substantiated. The objective of this study was to directly investigate the role of TLR3 in CVB-triggered T1DM in nonobese diabetic (NOD) mice, a mouse model of human T1DM that is widely used to study both spontaneous autoimmune and viral-induced T1DM...
February 2015: Endocrinology
Glen R Gallagher, Michael A Brehm, Robert W Finberg, Bruce A Barton, Leonard D Shultz, Dale L Greiner, Rita Bortell, Jennifer P Wang
Type 1 diabetes (T1D) is characterized by the destruction of the insulin-producing β-cells of pancreatic islets. Genetic and environmental factors both contribute to T1D development. Viral infection with enteroviruses is a suspected trigger for T1D, but a causal role remains unproven and controversial. Studies in animals are problematic because of species-specific differences in host cell susceptibility and immune responses to candidate viral pathogens such as coxsackievirus B (CVB). In order to resolve the controversial role of viruses in human T1D, we developed a viral infection model in immunodeficient mice bearing human islet grafts...
April 2015: Diabetes
Jana Precechtelova, Maria Borsanyiova, Darina Stipalova, Sona Sarmirova, Pavol Gomolcak, Katarina Berakova, Shubhada Bopegamage
Coxsackievirus B4 strain E2 (CVB4-E2) and its association with type 1 diabetes (T1D) have been studied in experimental in vitro and in vivo murine models. CVB4-E2, known to be pancreotropic and diabetogenic in nature, is associated with acute pancreatitis in mice but shows differences in the induction of glycemia after intraperitoneal (i.p.) infection. Therefore, the aim of this work was to study the outcome of oral infection with CVB4-E2 in five mouse strains with different genetic backgrounds: two outbred (Swiss albino, CD1), two inbred (SJL, NOD) and one transgenic (NOD...
January 2015: Archives of Virology
Xiaoling Tian, Yong Zhang, Suyi Gu, Yaochun Fan, Qiang Sun, Bo Zhang, Shaohong Yan, Wenbo Xu, Xueen Ma, Wenrui Wang
Hand, foot, and mouth disease (HFMD) surveillance was initiated in the Inner Mongolia Autonomous Region of China in 2007, a crucial scrutiny for monitoring the prevalence of enterovirus serotypes associated with HFMD patients. However, this surveillance mostly focused on enterovirus 71 (EV-A71) and coxsackievirus A16; therefore, information on other enterovirus serotypes is limited. To identify the other circulating enterovirus serotypes in the HFMD outbreaks in Inner Mongolia in 2010, clinical samples from HFMD patients were investigated...
2014: PloS One
Ming Hong Yen, Jia Jung Lee, Chia Feng Yeh, Kuo Chih Wang, Ya Wen Chiang, Lien Chai Chiang, Jung San Chang
ETHNOPHARMACOLOGICAL RELEVANCE: Yakammaoto is a prescription of traditional Chinese medicine (TCM) containing nine ingredients, including Ephedra sinica, Pinellia ternate, Zingiber officinale, Tussilago farfara, Aster tataricus, Ziziphus jujube, Belamcanda chinensis, Asarum sieboldii, and Schisandra chinensis. Yakammaoto has been used against flu-like symptoms for more than two thousand years in China and Japan. Coxsackievirus B4 (CVB4) causes not only flu-like symptoms but life-threatening diseases, such as pneumonia, acute kidney injury, and so forth with severe morbidity and mortality...
February 12, 2014: Journal of Ethnopharmacology
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