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Zu-Mu Zhou, Yi Xu, Cai-Song Hu, Qiong-Jiao Pan, Jing-Jiao Wei
This study aimed to analyze the epidemiological characteristics of hand, foot and mouth disease (HFMD) during 2008-14 in Wenzhou, China. The epidemiological data of HFMD retrieved from the Wenzhou Center for Disease Control and Prevention were retrospectively analyzed. HFMD infections with enterovirus 71 (EV71), Cox A16 or other pathogens were further verified by polymerase chain reaction (PCR) and real-time PCR. A total of 213 617 cases of HFMD were reported between 2008 and 2014 in Wenzhou. The average incidence was 384...
October 19, 2016: Journal of Tropical Pediatrics
Yajie Hu, Jie Song, Longding Liu, Jing Li, Beibei Tang, Jingjing Wang, Xiaolong Zhang, Ying Zhang, Lichun Wang, Yun Liao, Zhanlong He, Qihan Li
Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) are the predominant pathogens of hand, foot, and mouth disease (HFMD). Although these viruses exhibit genetic homology, the clinical manifestations caused by the two viruses have some discrepancies. In addition, the underlying mechanisms leading to these differences remain unclear. microRNAs (miRNAs) participate in numerous biological or pathological processes, including host responses to viral infections. Here, we focused on differences in miRNA expression patterns in rhesus monkey peripheral blood mononuclear cells (PBMCs) infected with EV71 and CA16 at various time points using high-throughput sequencing...
October 17, 2016: International Journal of Biochemistry & Cell Biology
Kan Xing Wu, Patchara Phuektes, Pankaj Kumar, Germaine Yen Lin Goh, Dimitri Moreau, Vincent Tak Kwong Chow, Frederic Bard, Justin Jang Hann Chu
Enterovirus 71 (EV71) is a neurotropic enterovirus without antivirals or vaccine, and its host-pathogen interactions remain poorly understood. Here we use a human genome-wide RNAi screen to identify 256 host factors involved in EV71 replication in human rhabdomyosarcoma cells. Enrichment analyses reveal overrepresentation in processes like mitotic cell cycle and transcriptional regulation. We have carried out orthogonal experiments to characterize the roles of selected factors involved in cell cycle regulation and endoplasmatic reticulum-associated degradation...
October 17, 2016: Nature Communications
Chengchao Chu, Shengxiang Ge, Jing Zhang, Huirong Lin, Gang Liu, Xiaoyuan Chen
We present a simple colorimetric assay for EV71 virus detection based on the aggregation of 4-mercaptobenzoic acid (4-MBA) and melamine (MA) modified silver nanoparticles (4-MBA-MA-AgNPs) in the presence of Mn(2+). The EV71-Ab1 was incubated on a 96-well plate and the EV71-Ab2 was labeled on the surface of three-dimensional nanoflower-like MnO2-PEG (3D-MnO2-PEG). After layer-by-layer immunoreactions, the EV71 virus and the corresponding 3D-MnO2-PEG-Ab2 were captured on the plate. With the addition of Vitamin C (Vc), Mn(2+) was released from the 3D-MnO2-PEG and then the aggregation of the 4-MBA-MA-AgNPs was induced, allowing a naked-eye detection limit of EV71 virus to be as low as 5 × 10(4) particles per mL, which is about three orders of magnitude lower than the conventional enzyme-linked immunosorbent assay (ELISA)...
September 15, 2016: Nanoscale
Huanru Wang, Liang Chang, Xiaohui Wang, Airong Su, Chunhong Feng, Yuxuan Fu, Deyan Chen, Nan Zheng, Zhiwei Wu
As a cytoplasmic parasite, RNA virus develops sophisticated mechanisms to counter host defense and utilize host proteins to facilitate its replication. Here we found Moloney leukemia virus 10 (MOV10), a highly conserved cellular protein belonging to SF1 helicase family, played critical roles in EV71 infection. Silencing cellular MOV10 could restrict EV71 replication, while over-expressing MOV10 resulted in increased viral replication at low dosage and repressed viral replication at high dosage. Further investigation showed that MOV10 exhibited dual functions in EV71 regulation, its C-terminus positively regulated viral replication by binding to EV71 cloverleaf-like structure and the internal ribosome entry site while the N-terminus showed a potential antiviral activity when individually overexpressed...
October 21, 2016: Biochemical and Biophysical Research Communications
Yong Wah Tan, Melgious Jin Yan Ang, Qiu Ying Lau, Anders Poulsen, Fui Mee Ng, Siew Wen Then, Jianhe Peng, Jeffrey Hill, Wan Jin Hong, Cheng San Brian Chia, Justin Jang Hann Chu
Hand, Foot and Mouth Disease is a highly contagious disease caused by a range of human enteroviruses. Outbreaks occur regularly, especially in the Asia-Pacific region, putting a burden on public healthcare systems. Currently, there is no antiviral for treating this infectious disease and the only vaccines are limited to circulation in China, presenting an unmet medical need that needs to be filled urgently. The human enterovirus 3 C protease has been deemed a plausible drug target due to its essential roles in viral replication...
2016: Scientific Reports
Huimin Gu, Dezhong Yin, Jie Ren, Baoliang Zhang, Qiuyu Zhang
Large size virion is unable to diffuse into pores of conventional porous chromatography particles. Therefore, separation of virion by conventional column-packing materials is not quite efficient. To solve this problem, a monolithic column with large convective pores and quaternary amine groups was prepared and was applied to separate Enterovirus 71 (EV71, ≈5700-6000kDa). Cross-section, pore structure, hydrodynamic performance, adsorption property and dynamic binding capacity of prepared monolithic column were determined...
October 15, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Ning Chen, Xingzhi Li, Pengfei Li, Ziye Pan, Yun Ding, Dehua Zou, Liang Zheng, Yating Zhang, Liyang Li, Lijie Xiao, Baifen Song, Yudong Cui, Hongwei Cao, Hua Zhang
Enterovirus 71 (EV71) is a human pathogen that induces hand, foot, and mouth disease (HFMD) and fatal neurological diseases in young children and infants. Pathogenicity of EV71 is likely related to its ability to evade host innate immunity through inhibiting cellular type I interferon signaling. However, it is less well understood the molecular events governing this process. In this study, we found that EV71 infection suppressed the induction of antiviral immunity by inhibiting the expression levels of IFN-β and IFN-stimulated genes (ISGs), such as ISG54 and ISG56, at the late stage of viral infection...
September 12, 2016: Microbial Pathogenesis
Yan Liu, Zhenhua Zheng, Bo Shu, Jin Meng, Yuan Zhang, Caishang Zheng, Xianliang Ke, Peng Gong, Qinxue Hu, Hanzhong Wang
: Accumulating evidences suggest that viruses hijack cellular proteins to circumvent the host immune system. Ubiquitination and SUMOylation are extensively studied post-translational modifications (PTMs) that play critical roles in diverse biological processes. Crosstalk between ubiquitination and SUMOylation of both host and viral proteins has been reported to result in distinct functional conses1quences. Enterovirus 71 (EV71), an RNA virus belonging to Picornaviridae family, is a common cause of hand, foot and mouth disease...
September 14, 2016: Journal of Virology
Jialei Sun, Jane Ennis, Jeffrey D Turner, Justin Jang Hann Chu
Enterovirus 71 (EV71) causes hand-foot-and-mouth diseases as well as neurological complications in young children. Interferon (IFN) can inhibit the replication of many viruses with low cytotoxic effects. Previously, an adenovirus vectored mouse interferon-α (DEF201), subtype 5, was generated by Wu et al, 2007. In this study, the antiviral effects of DEF201 against EV71 were evaluated in a murine model. 6-day-old BALB/c mice were administered a single dose of DEF201 before or after infection with lethal dose of EV71...
October 2016: Antiviral Research
Lin Liu, Yongping Ma, Huicong Zhou, Mingjun Wu
The nontoxic heat-labile toxin (LT) B subunit (LTB) was used as mucosal adjuvant experimentally. However, the mechanism of LTB adjuvant was still unclear. The LTB and enterovirus 71 (EV71) VP1 subunit (EVP1) were constructed in pET32 and expressed in E. coli BL21, respectively. The immunogenicity of purified EVP1 and the adjuvanticity of LTB were evaluated via intranasal immunization EVP1 plus LTB in Balb/c mice. In order to elucidate the proteome change triggered by the adjuvant of LTB, the proteomic profiles of LTB, EVP1, and LTB plus EVP1 were quantitatively analyzed by iTRAQ-LC-MS/MS (isobaric tags for relative and absolute quantitation; liquid chromatography-tandem mass spectrometry) in murine macrophage RAW264...
2016: International Journal of Molecular Sciences
Ping-Chin Chang, Shou-Chien Chen, Kow-Tong Chen
Enterovirus 71 (EV71) infections have a major public health impact in the Asia-Pacific region. We reviewed the epidemiology, pathogenesis, and molecular epidemiology of EV71 infection as well as EV71 vaccine development. Previous studies were found using the search terms "enterovirus 71" and "epidemiology" or "pathogenesis" or "molecular epidemiology" or "vaccine" in Medline and PubMed. Articles that were not published in the English language, manuscripts without an abstract, and opinion articles were excluded from the review...
2016: International Journal of Environmental Research and Public Health
Yangyang Zhai, Yuying Ma, Fei Ma, Quandeng Nie, Xuejiao Ren, Yaxin Wang, Luqing Shang, Zheng Yin
A series of peptidomimetic aldehydes were designed, synthesized, and evaluated for their biochemical activity against 3C protease (3C(pro)) and anti-enterovirus 71 (EV71) activity in vitro. Molecular docking revealed that 5s (IC50 = 0.22 ± 0.07 μM, EC50 = 0.18 ± 0.05 μM) could bind well to the active site of EV71 3C(pro), which was consistent with the biological data compared to reference 5a (IC50 = 0.54 ± 0.02 μM, EC50 = 0.26 ± 0.07 μM). Structure and relationship study led to the discovery of aldehyde 5x (IC50 = 0...
August 28, 2016: European Journal of Medicinal Chemistry
Fengwen Xu, Xiaoxiao Zhao, Siqi Hu, Jian Li, Lijuan Yin, Shan Mei, Tingting Liu, Ying Wang, Lili Ren, Shan Cen, Zhendong Zhao, Jianwei Wang, Qi Jin, Chen Liang, Bin Ai, Fei Guo
Enterovirus 71 (EV71) infection causes hand-foot-and-mouth disease that leads to cardiopulmonary complications and death in young children. There is thus an urgent need to find new treatments to control EV71 infection. In this study, we report potent inhibition of EV71 by a polyene antibiotic Amphotericin B. Amphotericin B profoundly diminished the expression of EV71 RNA and viral proteins in the RD cells and the HEK293 cells. As a result, EV71 production was inhibited by Amphotericin B with an EC50 (50% effective concentration) of 1...
2016: Scientific Reports
Guangyou Zhang, Jiwen Wang, Guo Yao, Baohai Shi
To investigate the efficacy of high-dose methylprednisolone pulse therapy in the treatment of Enterovirus 71 (EV71) encephalitis. To determine whether high-dose methylprednisolone pulse therapy should be used, 80 cases of pediatric patients with EV71 encephalitis were randomly divided into steroid pulse therapy group and non-steroid pulse therapy group and their clinical information was compared using statistic analysis. There was no statistical difference in the duration of fever, duration of nervous system involvement, duration of hospital stay, blood pressure, and cure rates between the two groups (p>0...
July 2016: Pakistan Journal of Pharmaceutical Sciences
Haolong Cong, Ning Du, Yang Yang, Lei Song, Wenliang Zhang, Po Tien
: To survive and replicate within a host, many viruses have evolved strategies that target crucial components within the apoptotic cascade, leading to either inhibition or induction of cell apoptosis. Enterovirus 71 (EV71) infections have been demonstrated to impact the mitochondrial apoptotic pathway and induce apoptosis in many cell lines. However, the detailed mechanism of EV71-induced apoptosis remains to be elucidated. In this study, we report that EV71 2B protein (2B) localized to the mitochondria and induced cell apoptosis by interacting directly with and activating the proapoptotic protein Bax...
November 1, 2016: Journal of Virology
Hye-Jin Kim, Ji-Yeon Hyeon, Seoyeon Hwang, Yong-Pyo Lee, Sang Won Lee, Jung Sik Yoo, Byunghak Kang, Jeong-Bae Ahn, Yong-Seok Jeong, June-Woo Lee
BACKGROUND: Enterovirus (EV) 71 is the main pathogen associated with hand, foot and mouth disease (HFMD) or herpangina. Outbreaks of HFMD caused by EV71 infection are associated severe neurological disease and high mortality rates in children. Several sporadic cases of EV71 infection occurred in the Republic of Korea (ROK) in 2000, and EV71 infections were not reported thereafter until 2006. In this prospective study, we report the epidemic and virologic characteristics of the EV71 endemic from 2007 to 2012 in the Republic of Korea...
2016: BMC Infectious Diseases
Juan Xu, Chunhua Zhang
Enterovirus (EV71) can cause severe neurological diseases, but the underlying pathogenesis remains unclear. The capsid protein, viral protein 1 (VP1), plays a critical role in the pathogenicity of EV71. High level expression and secretion of VP1 protein are necessary for structure, function and immunogenicity in its natural conformation. In our previous studies, 5 codon-optimized VP1 DNA vaccines, including wt-VP1, tPA-VP1, VP1-d, VP1-hFc and VP1-mFc, were constructed and analyzed. They expressed VP1 protein, but the levels of secretion and immunogenicity of these VP1 constructs were significantly different (P<0...
May 2016: Journal of Biomedical Research
Hong-Tao Zhou, Yong-Hui Guo, Man-Jun Chen, Yu-Xian Pan, Lin Xue, Bin Wang, Shao-Hua Tao, Nan Yu
BACKGROUND: Enterovirus (EV)-related hand, foot, and mouth disease/herpangina (HFMD/HA) has been prevalent in Guangdong Province, China, since 2010. METHODS: Clinical data for EV-related HFMD/HA inpatients admitted to the Department of Paediatrics of Zhujiang Hospital from 2010 to 2013 were retrospectively reviewed. The corresponding EV serotypes were also determined by reverse transcription-polymerase chain reaction or BLAST analysis of the sequenced partial lengths of the viral protein1/5'-untranslated region...
2016: BMC Infectious Diseases
An-Ting Liou, Szu-Yao Wu, Chun-Che Liao, Ya-Shu Chang, Chih-Shin Chang, Chiaho Shih
Enterovirus 71 (EV71) is a major threat to children worldwide. Children infected with EV71 could develop subclinical infection and hand-foot-and -mouth disease (HFMD). In severe cases, patients could develop encephalitis, paralysis, pulmonary edema, and death. A more user-friendly and robust animal model is essential to investigating EV71 pathogenesis. Here, we established a hybrid (hSCARB2(+/+)/stat-1(-/-)) mouse strain from crossbreeding SCARB2 transgenic and stat-1 KO mice, and compared the susceptibilities to EV71 infection and pathogenesis between parental and hybrid mice...
2016: Scientific Reports
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