scholarly journals SAMHD1 inhibits multiple Enteroviruses by interfering with the interaction between VP1 and VP2 proteins

2021 ◽  
Author(s):  
Zhilei Zhao ◽  
Zhaolong Li ◽  
Chen Huan ◽  
Xin Liu ◽  
Wenyan Zhang
Keyword(s):  
Binding Site ◽  
Biological Activities ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Viral Assembly ◽  
Inhibitory Effect ◽  
Coxsackievirus A6 ◽  
Enterovirus D68 ◽  
Acid Domain ◽  
Underlying Mechanisms

Sterile alpha motif and histidine-aspartic acid domain-containing protein 1 (SAMHD1) possess multiple biological activities such as virus restriction, innate immunity regulation, and autoimmunity. Our previous study demonstrated that SAMHD1 potently inhibits the replication of enterovirus 71 (EV71). In this study, we observed that SAMHD1 also restricts multiple enteroviruses (EVs) including Coxsackievirus A16 (CA16) and Enterovirus D68 (EVD68), but not Coxsackievirus A6 (CA6). Mechanistically, SAMHD1 competitively interacted with the same domain in VP1 that binds to VP2 of EV71 and EVD68, thereby interfering with the interaction between VP1 and VP2, and therefore viral assembly. Moreover, we showed that while the SAMHD1 T592A mutant maintained the EV71 inhibitory effect by attenuating the interaction between VP1 and VP2, the T592D mutant failed to. We also demonstrated that SAMHD1 could not inhibit CA6 because a different binding site is required for the SAMHD1 and VP1 interaction. Our findings reveal the mechanism of SAMHD1 inhibition of multiple EVs, and this could potentially be important for developing drugs against a broad range of EVs. Importance Enterovirus cause a wide variety of diseases, such as the hand-foot-and-mouth disease (HFMD), which is a severe public problem threatening children under 5 years. Therefore, identifying essential genes which restrict EV infection and exploring the underlying mechanisms is necessary to develop an effective strategy to inhibit EV infection. In this study, we report that host restrictive factor SAMHD1 has broad-spectrum antiviral activity against EV71, CA16 and EVD68 independent of its well-known dNTPase or RNase activity. Mechanistically, SAMHD1 restricts EVs by competitively interacting with the same domain in VP1 that binds to VP2 of EVs, thereby interfering with the interaction between VP1 and VP2, and therefore viral assembly. In contrast, we also demonstrated that SAMHD1 could not inhibit CA6 because a different binding site is required for the SAMHD1 and CA6 VP1 interaction. Our study reveals a novel mechanism for the SAMHD1 anti-EV replication activity.

Prevalence of Coxsackievirus A6 and Enterovirus 71 in Hand, Foot and Mouth Disease in Nanjing, China in 2013

2015 ◽  
Vol 34 (9) ◽  
pp. 951-957 ◽  
Author(s):  
Ya-Qian Hu ◽  
Guang-Cheng Xie ◽  
Dan-Di Li ◽  
Li-Li Pang ◽  
Jing Xie ◽  
...  
Keyword(s):  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Coxsackievirus A6 ◽  
Foot And Mouth

scholarly journals Inhibitory Effect and Mechanism of Arctium lappa Extract on NLRP3 Inflammasome Activation

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Young-Kyu Kim ◽  
Sushruta Koppula ◽  
Do-Wan Shim ◽  
Eun-Jung In ◽  
Su-Bin Kwak ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Biological Activities ◽  
Inhibitory Effect ◽  
Inflammasome Activation ◽  
Inhibitory Effects ◽  
Arctium Lappa ◽  
Nlrp3 Inflammasome Activation ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Peritonitis Model

Arctium lappa (A. lappa), Compositae, is considered a potential source of nutrition and is used as a traditional medicine in East Asian countries for centuries. Although several studies have shown its biological activities as an anti-inflammatory agent, there have been no reports on A. lappa with regard to regulatory role in inflammasome activation. The purpose of this study was to investigate the inhibitory effects of A. lappa extract (ALE) on NLRP3 inflammasome activation and explore the underlying mechanisms. We found that ALE inhibited IL-1β secretion from NLRP3 inflammasome activated bone marrow derived macrophages but not that secreted by NLRC4 and AIM2 inflammasomes activation. Mechanistic studies revealed that ALE suppressed the ATPase activity of purified NLRP3 and reduced mitochondrial reactive oxygen species (mROS) generated during NLRP3 activation. Therefore, the inhibitory effect of ALE on NLRP3 inflammasome might be attributed to its ability to inhibit the NLRP3 ATPase function and attenuated the mROS during inflammasome activation. In addition, ALE significantly reduced the LPS-induced increase of plasma IL-1β in mouse peritonitis model. These results provide evidence of novel anti-inflammatory mechanisms of A. lappa, which might be used for therapeutic applications in the treatment of NLRP3 inflammasome-associated inflammatory disorders.

scholarly journals Treatment of Herpangina Patients with Xiyanping Injection: A Retrospective Study Based on the Hospital Electronic Medical Record System

2021 ◽  
Author(s):  
Hongjiao Geng ◽  
Ruili Wei ◽  
Zhifei Wang ◽  
Yanming Xie ◽  
Zhishuai Liu
Keyword(s):  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Electronic Medical Record System ◽  
Inhibitory Effects ◽  
Multiple Sources ◽  
Record System ◽  
Medical Record System ◽  
Underlying Mechanisms ◽  
Main Components ◽  
Medical Advances

Abstract Background: Although we have made tremendous medical advances in recent decades in vaccine and supportive therapies, the treatment of herpangina has not experienced such rapid advancement. Xiyanping injection(XYP) is a Chinese prescription with andrographolide as the main components. XYP shows strong inhibitory effects against enterovirus 71 virus,and existence of dose-response relationships in pharmacology studies. However, herpangina still lack specific therapeutics. The present study aimed to demonstrate the “real-world” experiences of herpangina in China using XYP therapy,to provide a basis for treatment of herpangina in children. Methods: We analyzed data of patients (≤70 years) diagnosed with herpangina and used XYP between October 2006 to October 2016 from the large electronic data warehouse (EDW), a multiple sources including hospital information system（HIS） data of “tertiary grade A hospitals” in China. Statistical analyses were performed by SAS9.2 and R.25 software. We present the following article in accordance with the STROBE Statement reporting checklist. Results: A total of 3423 patients of herpangina were retrieved for the analysis in this study. The mean age of the patient population was 2.66 years. Herpangina patients are often with multiple diagnosis, of which hand-foot-and-mouth disease(HFMD), bronchopneumonia and febrile seizure present a higher probability. Antibiotics were the most prescribed (17.61%) except for XYP, followed by ascorbate (10.40%). Conclusions: This study is the first comprehensive retrospective review of herpangina for XYP that has been used in a clinical setting. The present findings of clinical characteristics are fairly consistent with previous clinical studies. Clinical medication use of herpangina were basically in accordance with Expert Consensus of Herpangina in China(2019).Meanwhile, there are abuse problems of antibiotics and antivirals. Despite the underlying mechanisms in antibacterial and antiviral of XYP, the exact clinical efficacy is yet to be revealed. The efficacy and safety of XYP with Western medicines has not been studied.

Coxsackievirus A6 and enterovirus 71 causing hand, foot and mouth disease in Cuba, 2011–2013

2014 ◽  
Vol 159 (9) ◽  
pp. 2451-2455 ◽  
Author(s):  
Magilé C. Fonseca ◽  
Luis Sarmiento ◽  
Sonia Resik ◽  
Yenisleidys Martínez ◽  
Lai Heng Hung ◽  
...  
Keyword(s):  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Coxsackievirus A6 ◽  
Foot And Mouth

scholarly journals Nobiletin Inhibits Cell Growth, Migration and Invasion, and Enhances the Anti-Cancer Effect of Gemcitabine on Pancreatic Cancer Cells

2021 ◽  
Vol 16 (4) ◽  
pp. 1934578X2110040
Author(s):  
Xiang Ren ◽  
Yuran Ma ◽  
Xiao Wang ◽  
Xuetao Xu ◽  
Panpan Wu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Pancreatic Cancer Cells ◽  
Underlying Mechanisms ◽  
Sphere Formation

Natural products are very promising adjuvants with a variety of biological activities. Nobiletin, a citrus polymethoxyflavone, has been shown to exert an anticancer effect in various cell lines. In this study, we investigated the effects of nobiletin on cell viability, sphere formation, migration and invasion of pancreatic cancer cells, and the underlying mechanisms. Our results demonstrate that nobiletin significantly inhibited PANC-1 cell migration and invasion, and these effects were associated with downregulation of MMP-2. We also found that nobiletin, in a low concentration, exhibited a strong inhibitory effect on sphere formation. The potential molecular mechanisms were related to significant downregulation of p-mTOR and p-STAT3. Furthermore, we found that nobiletin combined with gemcitabine synergistically inhibited PANC-1 cell viability and sphere formation. The underlying mechanisms of the synergistic inhibition on growth were associated with decreases in p-STAT3 expression. Overall, our results suggest that nobiletin may be a promising candidate for pancreatic cancer adjuvant treatment.

scholarly journals Surveillance, Epidemiology and Impact of EV-A71 Vaccination on Hand, Foot, and Mouth Disease in Nanchang, China, 2010–2019

2022 ◽  
Vol 12 ◽  
Author(s):  
Fenglan He ◽  
Jia Rui ◽  
Zhiqiang Deng ◽  
Yanxia Zhang ◽  
Ke Qian ◽  
...  
Keyword(s):  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Surveillance Network ◽  
Coxsackievirus A6 ◽  
Foot And Mouth ◽  
Native Strains ◽  
Autumn And Winter ◽  
The Impact ◽  
Pathogen Spectrum

After the first national-scale outbreak of Hand, foot, and mouth disease (HFMD) in China, a national surveillance network was established. Here we described the epidemiology and pathogenic profile of HFMD and the impact of EV-A71 vaccination on pathogen spectrum of enteroviruses in the southeastern Chinese city of Nanchang during 2010–2019. A total of 7,951 HFMD cases from sentinel hospitals were included, of which 4,800 EV-positive cases (60.4%) were identified by real-time RT-PCR. During 2010–2012, enterovirus 71 (EV-A71) was the main causative agent of HFMD, causing 63.1% of cases, followed by 19.3% cases associated with coxsackievirus A16 (CV-A16). Since 2013, the proportion of other enteroviruses has increased dramatically, with the sub genotype D3 strain of Coxsackievirus A6 (CV-A6) replacing the dominance of EV-A71. These genetically diverse native strains of CV-A6 have co-transmitted and co-evolved in Nanchang. Unlike EV-A71 and CV-A16, most CV-A6 infections were concentrated in autumn and winter. The incidence of EV-A71 infection negatively correlated with EV-A71 vaccination (r = −0.990, p = 0.01). And severe cases sharply declined as the promotion of EV-A71 vaccines. After 2-year implementation of EV-A71 vaccination, EV-A71 is no longer detected from the reported HFMD cases in Nanchang. In conclusion, EV-A71 vaccination changed the pattern of HFMD epidemic, and CV-A6 replaced the dominance of EV-A71 over time.

ENTEROVIRUS INFECTION: OVERVIEW OF THE CURRENT GLOBAL SITUATION IN THE CONTEXT OF INTENSIFIED MIGRATION FLOWS

2018 ◽  
pp. 55-60
Author(s):  
L.V. Butakova ◽  
O.E. Trotsenko ◽  
E.Yu. Sapega
Keyword(s):  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Foot And Mouth Disease ◽  
Scientific Data ◽  
Enterovirus Infection ◽  
Coxsackievirus A6 ◽  
Golden Standard ◽  
Enterovirus D68 ◽  
Genetic Techniques ◽  
Migration Flows

The review presents data on epidemiological risks concerning worldwide spread of enterovirus infection due to intensified migration flows. Outbreak incidence of the most frequently registered forms of enterovirus infection – hand, foot and mouth disease (HFMD) –was analyzed. At the present time, Coxsackievirus A6 plays ever-greater significance in HFMD incidence. The article summarizes currently available scientific data on atypical Coxsackievirus A6-infection clinical manifestations. Details on the tense epidemiological situation concerning Enterovirus D68 that can be the cause of acute flaccid paralysis/myelitis are presented. According to latest recommendations, the molecular genetic techniques are the «golden standard» in diagnostics of enterovirus infection.

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