scholarly journals A Laboratory Evaluation of Medicinal Herbs Used in China for the Treatment of Hand, Foot, and Mouth Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaoqing Chen ◽  
Chunyang Wang ◽  
Lanfang Xu ◽  
Xiaoshuang Chen ◽  
Wei Wang ◽  
...  
Keyword(s):  
Viral Infection ◽  
Enterovirus 71 ◽  
Water Extract ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Chinese Herbs ◽  
Ev71 Infection ◽  
Laboratory Evaluation ◽  
Proinflammatory Response ◽  
Foot And Mouth

Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the causative agents of hand, foot, and mouth disease (HFMD). During recent epidemics of HFMD in China, medicinal herbals and preparations containing herbal extracts have demonstrated therapeutic efficacy with relative safety profiles. There have been no microbiological studies to validate their usefulness for HFMD. We selected 12 commonly used herbs for HFMD from government recommended guidelines as well as published reports and tested for their antiviral activity and anti-inflammatory activity. A water extract ofHouttuynia cordataThunb. (HCT) inhibited EV71 infection significantly and was marginally active against CVA16 infection. The IC50(concentration to have 50% inhibitory effect) values of HCT against a Fuyang strain and a BrCr strain of EV71 were determined at 8.9 μg/mL and 20.6 μg/mL, respectively.Mentha haplocalyxBriq. (MHB) water extract was active against CVA16, with an IC50value of 70.3 μg/mL. The extract did not exhibit activity against EV71 infection. Although the majority of the extracts showed no activity against viral infection, several extracts demonstrated activity in blocking proinflammatory response by viral infection. This study therefore validates the effectiveness of Chinese herbs for HFMD since some formulations containing the correct combination of the herbs can block viral replication as well as proinflammatory response of HFMD.

scholarly journals Increased Frequency of Circulating Follicular Helper T Cells in Children with Hand, Foot, and Mouth Disease Caused by Enterovirus 71 Infection

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Jianping Wu ◽  
David Cui ◽  
Xianzhi Yang ◽  
Jianzhou Lou ◽  
Jie Lin ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Serum Levels ◽  
Mouth Disease ◽  
Ev71 Infection ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Foot And Mouth

Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD) in children. The role of T follicular helper (TFH) cells in EV71-infected children remains unclear in regulating humoral immunity. The frequency of circulating ICOShigh/PD-1highCXCR5+CD4+TFH cells in the children with mild and severe EV71 infection and healthy controls (HC) was detected by flow cytometry, respectively. IL-21 and IL-6 mRNA expression and their serum levels, Bcl-6 mRNA expression, and specific neutralizing antibodies against EV71 (NAb-EV71) were measured. In the acute stage of patients with EV71 infection, increased frequencies of circulating TFH cells with ICOShighand PD-1highexpression in the mild and severe patients were observed, and the positive correlations among the frequencies of circulating TFH cells and the serum levels of IL-21, IL-6, and NAb-EV71 titres were detected, respectively. Moreover, the expressions of IL-6 and IL-21 mRNA in PBMCs from patients were also significantly higher than those of HC. However, further analysis did not reveal any significant differences between mild and severe patients. These data indicate a role of TFH cells and associated cytokines in modulating the humoral response during the pathogenesis of EV71 infection.

scholarly journals Fibronectin Facilitates Enterovirus 71 Infection by Mediating Viral Entry

2018 ◽  
Vol 92 (9) ◽  
Author(s):  
Qiao-qiao He ◽  
Sheng Ren ◽  
Zhang-chuan Xia ◽  
Zhi-kui Cheng ◽  
Nan-fang Peng ◽  
...  
Keyword(s):  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Host Factor ◽  
Mouth Disease ◽  
Host Cells ◽  
Ev71 Infection ◽  
Human Enterovirus ◽  
Human Enterovirus 71 ◽  
Viral Yield ◽  
Foot And Mouth

ABSTRACTFibronectin (FN) is a high-molecular-weight extracellular matrix protein that contains the RGDS motif, which is required to bind to integrins. Synthetic RGDS peptides have been reported to compete with FN to bind to the cell surface and inhibit the function of FN. Here, we identified that synthetic RGDS peptides significantly inhibit human enterovirus 71 (EV71) infection in cell cultures. In addition, mice treated with RGDS peptides and infected with EV71 had a significantly higher survival rate and a lower viral load than the control group. Because RGDS peptides affect the function of FN, we questioned whether FN may play a role in virus infection. Our study indicates that overexpression of FN enhanced EV71 infection. In contrast, knockout of FN significantly reduced viral yield and decreased the viral binding to host cells. Furthermore, EV71 entry, rather than intracellular viral replication, was blocked by FN inhibitor pretreatment. Next, we found that FN could interact with the EV71 capsid protein VP1, and further truncated-mutation assays indicated that the D2 domain of FN could interact with the N-terminal fragment of VP1. Taken together, our results demonstrate that the host factor FN binds to EV71 particles and facilitates EV71 entry, providing a potential therapy target for EV71 infection.IMPORTANCEHand, foot, and mouth disease outbreaks have occurred frequently in recent years, sometimes causing severe neurological complications and even death in infants and young children worldwide. Unfortunately, no effective antiviral drugs are available for human enterovirus 71 (EV71), one of the viruses that cause hand, foot, and mouth disease. The infection process and the host factors involved remain unknown, although several receptors have been identified. In this study, we found that the host factor fibronectin (FN) facilitated EV71 replication by interacting with EV71 particles and further mediated their entry. The RGDS peptide, an FN inhibitor, significantly inhibited EV71 replication in both RD cells and mice. In conclusion, our research identified a new host factor involved in EV71 infection, providing a new potential antiviral target for EV71 treatment.

scholarly journals Sporadic Hand, Foot and Mouth Disease Cases Associated With Non-C4 Enterovirus 71 Strain in Xiamen, China From 2009-2018

2021 ◽  
Author(s):  
Mengyuan Chen ◽  
Shuizhen He ◽  
Qiang Yan ◽  
Jianmei Zhang ◽  
Caiyu Li ◽  
...  
Keyword(s):  
Young Children ◽  
Nested Pcr ◽  
Mainland China ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Ev71 Infection ◽  
Foot And Mouth ◽  
Almost All

Abstract EV71 has caused large HFMD epidemics among young children and EV71 infection was the leading cause of severe cases and deaths. In mainland China, almost all EV71 strains were segregated into C4 sub-genotype and prevalence of non-C4 EV71 strains was still unclear in mainland China. This study aimed to comprehensively report this in Xiamen. 5’UTR and VP1 Sequences of the strains were amplified by RT-nested-PCR and then sequenced. 32 non-C4 EV71 strains were identified in Xiamen during the study. This study would provide important information for related fields and provide new insights of EV71 strains in China.

HAND, FOOT AND MOUTH DISEASE IN SOUTH BENGAL AND KOLKATA: A STUDY OVER 5 YEARS TO EVALUATE CASES WITH CLINICAL SUSPICION

2021 ◽  
pp. 39-41
Author(s):  
Swagnik Roy ◽  
Bibhas SahaDalal ◽  
Rajat Dasgupta ◽  
Sourabh Mitra ◽  
Amrita Roy ◽  
...  
Keyword(s):  
Disease Risk ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Ev71 Infection ◽  
Human Enterovirus ◽  
Neurological Involvement ◽  
Neurogenic Pulmonary Edema ◽  
Foot And Mouth ◽  
Hands And Feet

Hand, foot, and mouth disease is a very infective infection. It's caused by viruses from the Enterovirus genus, among the Enterovirus genus coxsackievirus is most commonly found associated with Hand , Foot and Mouth disease. Hand, foot and mouth disease (HFMD) causes rashes or vesicular lesions in the affected individuals and lesions are found in extremities and upper extremity lesion is more common along with feet and mouth. It is mostly seen in school going children, and causative agents are likely Enterovirus-A (EV-A) species, including Coxsackievirus-A16 (CV-A16) and Enterovirus-71 (EV-71) [1]. Hand , Foot and Mouth Disease is usullay mild and selimiting. In the affected patient's rst identied by a brief prodromal fever, followed by pharyngitis, mouth ulcers and rash on the hands and feet. The disease is caused by numerous members of the Enterovirus genus of the family Picornaviridae e.g. Coxsackievirus type A (CA) and Enterovirus 71 (EV71), and the clinical features are not identiable and distinguishable from virus to virus. [2] . Young children have the highest risk of getting hand, foot, and mouth disease. Risk increases if they attend daycare or school, as viruses can spread quickly in these facilities. Children usually build up immunity to the disease after being exposed to the viruses that cause it. This is why the condition rarely affects people over age 10. However, it's still possible for older children and adults to get the infection, especially if they have weakened immune systems. EV71 is a human enterovirus A species causing infection in clildren[3,4] . Clinically though it is mild symptoms and self limiting initially, such as a fever along with unraised colorless spots, and bumps on the hands, feet, and mouth. In some patients with severe disease several neurological complications (including cephalomeningitis, encephalitis, and neurogenic pneumonedema) and circulatory disorders. Occasionally, it even causes death [5]. Therefore, an early indicator of EV71 infection with neurological involvement is crucial for appropriate management [6]. Hand, foot, and mouth disease by enterovirus infection repots severe complications (such as brain stem encephalitis, neurogenic pulmonary edema, and other fatal complications) and a high mortality due to HFMD are more frequently related to EV71 infection[7,8] .

scholarly journals Predicting Severe Enterovirus 71-Infected Hand, Foot, and Mouth Disease: Cytokines and Chemokines

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Weijian Zhang ◽  
Zhigang Huang ◽  
Mingyuan Huang ◽  
Jincheng Zeng
Keyword(s):  
Immune Responses ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Ev71 Infection ◽  
Research Teams ◽  
Host Immune Responses ◽  
Cytokines And Chemokines ◽  
Foot And Mouth ◽  
Infants And Young Children

Enterovirus 71 (EV71) is one of the most common intestinal virus that causes hand, foot, and mouth disease (HFMD) in infants and young children (mostly ≤5 years of age). Generally, children with EV71-infected HFMD have mild symptoms that resolve spontaneously within 7-14 days without complications. However, some EV71-infected HFMD cases lead to severe complications such as aseptic meningitis, encephalitis, acute flaccid paralysis, pulmonary edema, cardiorespiratory complication, circulatory disorders, poliomyelitis-like paralysis, myocarditis, meningoencephalitis, neonatal sepsis, and even death. The mechanism of EV71 pathogenesis has been studied extensively, and the regulation of host immune responses is suspected to aggravate EV71-induced severe complications. Recently, several cytokines or chemokines such as TNF-α, IFN-γ, IL-1β, IL-18, IL-33, IL-37, IL-4, IL-13, IL-6, IL-12, IL-23, IL-27, IL-35, IL-10, IL-22, IL-17F, IL-8, IP-10, MCP-1, G-CSF, and HMGB1 have been reported to be associated with severe EV71 infection by numerous research teams, including our own. This review is aimed at summarizing the pathophysiology of the cytokines and chemokines with severe EV71 infection.

scholarly journals In VitroandIn VivoInhibition of the Infectivity of Human Enterovirus 71 by a Sulfonated Food Azo Dye, Brilliant Black BN

2019 ◽  
Vol 93 (17) ◽  
Author(s):  
Tao Meng ◽  
Qiang Jia ◽  
Sek-Man Wong ◽  
Kaw-Bing Chua
Keyword(s):  
Azo Dyes ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Antiviral Drugs ◽  
Mouth Disease ◽  
Ev71 Infection ◽  
Human Enterovirus ◽  
Dependent Manner ◽  
Human Enterovirus 71 ◽  
Foot And Mouth

ABSTRACTHand, foot, and mouth disease (HFMD), a highly contagious disease in children, is caused by human enteroviruses, including enterovirus 71 (EV71), coxsackievirus A16 (CVA16), and coxsackievirus A6 (CVA6). Although HFMD is usually mild and self-limiting, EV71 infection occasionally leads to fatal neurological disorders. Currently, no commercial antiviral drugs for HFMD treatment are available. Here, numerous sulfonated azo dyes, widely used as food additives, were identified as having potent antiviral activities against human enteroviruses. Among them, brilliant black BN (E151) was able to inhibit all EV71, CVA16, and CVA6 strains tested. In rhabdomyosarcoma cells, the 50% inhibitory concentrations of the dye E151 for various strains of EV71 ranged from 2.39 μM to 28.12 μM, whereas its 50% cytotoxic concentration was 1,870 μM. Food azo dyes, including E151, interacted with the vertex of the 5-fold axis of EV71 and prevented viral entry. Their efficacy in viral inhibition was regulated by amino acids at VP1-98, VP1-145, and/or VP1-246. Dye E151 not only prevented EV71 attachment but also eluted attached viruses in a concentration-dependent manner. Moreover, E151 inhibited the interaction between EV71 and its cellular uncoating factor cyclophilin A.In vivostudies demonstrated that E151 at a dose of 200 mg/kg of body weight/day given on the initial 4 days of challenge protected AG129 mice challenged with 10× the 50% lethal dose of wild-type EV71 isolates. Taken together, these data highlight E151 as a promising antiviral agent against EV71 infection.IMPORTANCEHuman enterovirus 71 (EV71) is one of the causative agents of hand, foot, and mouth disease in children and is responsible for thousands of deaths in the past 20 years. Food azo dyes have been widely used since the nineteenth century; however, their biological effects on humans and microbes residing in humans are poorly understood. Here, we discovered that one of these dyes, brilliant black BN (E151), was particularly effective in inhibiting the infectivity of EV71 in both cell culture and mouse model studies. Mechanistic studies demonstrated that these sulfonated dyes mainly competed with EV71 attachment factors for viral binding to block viral attachment/entry to host cells. As no commercial antiviral drugs against EV71 are currently available, our findings open an avenue to exploit the development of permitted food dye E151 as a potential anti-EV71 agent.

scholarly journals DNA methylation and SNP in IFITM3 are correlated with hand, foot and mouth disease caused by enterovirus 71

2021 ◽  
Vol 105 ◽  
pp. 199-208
Author(s):  
Mei Li ◽  
Ya-Ping Li ◽  
Hui-Ling Deng ◽  
Mu-Qi Wang ◽  
Yuan Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Foot And Mouth

scholarly journals Advances in Antigenic Peptide-Based Vaccine and Neutralizing Antibodies against Viruses Causing Hand, Foot, and Mouth Disease

2019 ◽  
Vol 20 (6) ◽  
pp. 1256 ◽  
Author(s):  
Mohd Anasir ◽  
Chit Poh
Keyword(s):  
Neutralizing Antibodies ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Antigenic Peptide ◽  
Effective Vaccine ◽  
Inactivated Vaccine ◽  
Antigenic Peptides ◽  
Foot And Mouth ◽  
Etiological Agents

Hand, foot, and mouth disease (HFMD) commonly produces herpangina, but fatal neurological complications have been observed in children. Enterovirus 71 (EV-A71) and Coxsackievirus 16 (CV-A16) are the predominant viruses causing HFMD worldwide. With rising concern about HFMD outbreaks, there is a need for an effective vaccine against EV-A71 and CV-A16. Although an inactivated vaccine has been developed against EV-A71 in China, the inability of the inactivated vaccine to confer protection against CV-A16 infection and other HFMD etiological agents, such as CV-A6 and CV-A10, necessitates the exploration of other vaccine platforms. Thus, the antigenic peptide-based vaccines are promising platforms to develop safe and efficacious multivalent vaccines, while the monoclonal antibodies are viable therapeutic and prophylactic agents against HFMD etiological agents. This article reviews the available information related to the antigenic peptides of the etiological agents of HFMD and their neutralizing antibodies that can provide a basis for the design of future therapies against HFMD etiological agents.

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