Enterovirus 71 infection in children with hand, foot, and mouth disease in Shanghai, China: epidemiology, clinical feature and diagnosis

Wang, Ying; Zou, Gang; Xia, Ai; Wang, Xiangshi; Cai, Jiehao; Gao, Qianqian; Yuan, Shilin; He, Guimei; Zhang, Shuyi; Zeng, Mei; Altmeyer, Ralf

doi:10.1186/s12985-015-0308-2

Cited by 45 publications

(42 citation statements)

References 38 publications

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“…The crystal structure of EV71 3Cpro has been determined and reported previously [39]. A flexible surface loop β-ribbon is important for recognition of the P2-P4 region of the peptide substrate.…”

Section: Interaction Between Quercetin and 3c Promentioning

confidence: 94%

Inhibition of enterovirus 71 replication and viral 3C protease by quercetin

Yao

et al. 2018

Virol J

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BackgroundEnterovirus 71 (EV71) is one of the major causative agents of hand, foot, and mouth disease (HFMD), which is sometimes associated with severe central nervous system disease in children. There is currently no specific medication for EV71 infection. Quercetin, one of the most widely distributed flavonoids in plants, has been demonstrated to inhibit various viral infections. However, investigation of the anti-EV71 mechanism has not been reported to date.MethodsThe anti-EV71 activity of quercetin was evaluated by phenotype screening, determining the cytopathic effect (CPE) and EV71-induced cells apoptosis. The effects on EV71 replication were evaluated further by determining virus yield, viral RNA synthesis and protein expression, respectively. The mechanism of action against EV71 was determined from the effective stage and time-of-addition assays. The possible inhibitory functions of quercetin via viral 2Apro, 3Cpro or 3Dpol were tested. The interaction between EV71 3Cpro and quercetin was predicted and calculated by molecular docking.ResultsQuercetin inhibited EV71-mediated cytopathogenic effects, reduced EV71 progeny yields, and prevented EV71-induced apoptosis with low cytotoxicity. Investigation of the underlying mechanism of action revealed that quercetin exhibited a preventive effect against EV71 infection and inhibited viral adsorption. Moreover, quercetin mediated its powerful therapeutic effects primarily by blocking the early post-attachment stage of viral infection. Further experiments demonstrated that quercetin potently inhibited the activity of the EV71 protease, 3Cpro, blocking viral replication, but not the activity of the protease, 2Apro, or the RNA polymerase, 3Dpol. Modeling of the molecular binding of the 3Cpro-quercetin complex revealed that quercetin was predicted to insert into the substrate-binding pocket of EV71 3Cpro, blocking substrate recognition and thereby inhibiting EV71 3Cpro activity.ConclusionsQuercetin can effectively prevent EV71-induced cell injury with low toxicity to host cells. Quercetin may act in more than one way to deter viral infection, exhibiting some preventive and a powerful therapeutic effect against EV71. Further, quercetin potently inhibits EV71 3Cpro activity, thereby blocking EV71 replication.

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Section: Interaction Between Quercetin and 3c Promentioning

confidence: 94%

Inhibition of enterovirus 71 replication and viral 3C protease by quercetin

Yao

et al. 2018

Virol J

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“…Previous studies indicated that attending childcare or kindergarten significantly increased the seropositive rates of anti-EV71 antibodies123. It has also been reported that epidemics of EV71 spread from schools to the community at large3637.…”

Section: Discussionmentioning

confidence: 98%

“…Hand, foot, and mouth disease (HFMD) is a commonly benign, febrile disease primarily affecting infants and young children and is characterized by ulcers on the mouth, hands, and/or feet123. HFMD is often associated with enteroviruses, most commonly enterovirus 71 (EV71) and coxsackievirus A16 (CVA16)45.…”

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confidence: 99%

“…In recent decades, HFMD has been recognized as an emerging public health issue across the Western Pacific region and especially in mainland China123. Hundreds of thousands of children develop HFMD each year in addition to recent outbreaks in Shanghai and Zunyi, with over 2,000,000 and 6,000 cases spanning one year, respectively123.…”

mentioning

confidence: 99%

“…Hundreds of thousands of children develop HFMD each year in addition to recent outbreaks in Shanghai and Zunyi, with over 2,000,000 and 6,000 cases spanning one year, respectively123. There are also sporadic HFMD outbreaks in East Asia, Southeast Asia and other regions since it was first reported in California, USA in 1969101112.…”

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confidence: 99%

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Characterization of enterovirus 71 infection and associated outbreak of Hand, Foot, and Mouth Disease in Shawo of China in 2012

Liu

Lai

et al. 2016

Sci Rep

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Infection of enterovirus 71 (EV71) and associated hand, foot, and mouth disease (HFMD) are recognized as emerging public health issues worldwide. Hundreds of thousands of children are annually infected with EV71 and develop HFMD in China alone. Studies of EV71 infection are critical to the treatment and prevention of the associated HFMD outbreaks. In this report, we studied an outbreak of 105 HFMD cases in Shawo Township of China between September to October 2012. More than 90% of cases were children younger than 9 years old, with over 50% of cases aged 3–6 years old. Laboratory studies detected a high prevalence of EV71 and suggested EV71 as the most common enterovirus causing HFMD in Shawo. Sequencing analysis showed that the EV71 strains from Shawo belong to the C4 subgenotype, and are phylogenetically more related to those from the distant city of Nanchang than those from the nearby city of Wuhan with distinct variations. More girls were found to be associated with EV71 in Shawo whereas more boys were associated with EV71 in Wuhan and Nanchang. Our studies further the understanding of the molecular epidemiological features of HFMD and infection by enteroviruses in China.

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Global epidemiology of nonpolio enteroviruses causing severe neurological complications: A systematic review and meta‐analysis

Suresh

Rawlinson

Andrews

et al. 2019

Reviews in Medical Virology

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Enteroviruses are RNA viruses found as commensals in the human gut and respiratory system, which may cause a wide spectrum of disease. Enteroviruses may cause severe neurologic complications including acute flaccid paralysis (AFP) and encephalitis and are the most commonly diagnosed agents of viral meningitis. Outbreaks of more severe disease are often associated with particular genotypes, such as enterovirus-A71 causing rhombencephalitis and AFP. There are more than 300 described genotypes of human enterovirus, with overlaps in clinical phenotypes between genotypes, and uncertainty about which genotypes are more prevalent in neurological manifestations.A systematic review of observational studies was conducted to evaluate the most prevalent enterovirus genotypes causing AFP, encephalitis, and meningitis. The genotyping methods and sampling sites were compiled as secondary outcomes.Sources included MEDLINE, Embase (publications until January 2019), and references selected from included studies. Meta-analyses using a random effects model were performed to calculate the pooled proportion of enterovirus genotypes in each disease.Ninety-six publications met the eligibility criteria, comprising 3779 AFP cases, 1140 encephalitis cases, and 32 810 meningitis cases. Enterovirus-A71 was most frequently associated with AFP (pooled proportion 0.12, 95% CI, 0.05-0.20) and encephalitis (0.77, 95% CI, 0.61-0.91). Echovirus 30 (0.35, 95% CI, 0.27-0.42) was the most predominant genotype in meningitis cases. Genotypes were most commonly determined using VP1 RT-reverse transcription-polymerase chain reaction, and most samples assessed were cerebrospinal fluid.With the emergence of enteroviruses as an increasing cause of neurological diseases, surveillance and testing need to increase to identify the aetiology of the most common and most severe disorders.

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Enterovirus 71 infection in children with hand, foot, and mouth disease in Shanghai, China: epidemiology, clinical feature and diagnosis

Cited by 45 publications

References 38 publications

Inhibition of enterovirus 71 replication and viral 3C protease by quercetin

Inhibition of enterovirus 71 replication and viral 3C protease by quercetin

Characterization of enterovirus 71 infection and associated outbreak of Hand, Foot, and Mouth Disease in Shawo of China in 2012

Global epidemiology of nonpolio enteroviruses causing severe neurological complications: A systematic review and meta‐analysis

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