Enterovirus Diseases and Vaccines

2021 ◽  
Author(s):  
Heinz-Josef Schmitt
Keyword(s):  
Disease Outbreaks ◽  
Foot And Mouth Disease ◽  
Asia Pacific ◽  
Asia Pacific Region ◽  
Internal Organs ◽  
Enterovirus A71 ◽  
Life Threatening ◽  
Development Pipeline ◽  
The Brain ◽  
Genus Enterovirus

Enterovirus A71 (EV A71) (genus enterovirus, family pircornaviridae) causes benign vesicular lesions on skin (hand, foot and mouth disease, HFMD) and mucous membranes of the mouth (herpangina), and also severe to life-threatening infections of the brain, the heart, and other internal organs. Disease outbreaks in the Asia-Pacific region regularly involve thousands of children <5 years resulting in many deaths. Such outbreaks are caused by specific EV genotypes that vary by time and place. While there are various promising and innovative options for treatment in development, none are licensed to date. Immunoglobulins may be beneficial through virus neutralization and modulation of the inflammatory response by the host. In China, 3 different highly efficacious and safe vaccines are commercially available; however, none are licensed outside the country. Roughly half a dozen vaccines are in the development pipeline, with some using innovative approaches and trying to broaden strain coverage.

scholarly journals Enterovirus A71: virulence, antigenicity, and genetic evolution over the years

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Sheng-Wen Huang ◽  
Dayna Cheng ◽  
Jen-Ren Wang
Keyword(s):  
Neurological Disease ◽  
Foot And Mouth Disease ◽  
Asia Pacific ◽  
Pacific Region ◽  
Genetic Evolution ◽  
Virulence Determinants ◽  
Global Public Health ◽  
Asia Pacific Region ◽  
Enterovirus A71 ◽  
Global Epidemiology

Abstract As a neurotropic virus, enterovirus A71 (EV-A71) emerge and remerge in the Asia-Pacific region since the 1990s, and has continuously been a threat to global public health, especially in children. Annually, EV-A71 results in hand-foot-and-mouth disease (HFMD) and occasionally causes severe neurological disease. Here we reviewed the global epidemiology and genotypic evolution of EV-A71 since 1997. The natural selection, mutation and recombination events observed in the genetic evolution were described. In addition, we have updated the antigenicity and virulence determinants that are known to date. Understanding EV-A71 epidemiology, genetic evolution, antigenicity, and virulence determinants can expand our insights of EV-A71 pathogenesis, which may benefit us in the future.

scholarly journals Adaptation and Virulence of Enterovirus-A71

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1661
Author(s):  
Kyousuke Kobayashi ◽  
Satoshi Koike
Keyword(s):  
Foot And Mouth Disease ◽  
Asia Pacific ◽  
Health Concern ◽  
Virulence Determinants ◽  
Future Perspectives ◽  
Asia Pacific Region ◽  
Public Health Concern ◽  
Host Environment ◽  
Multiple Receptors ◽  
Enterovirus A71

Outbreaks of hand, foot, and mouth disease caused by enterovirus-A71 (EV-A71) can result in many deaths, due to central nervous system complications. Outbreaks with many fatalities have occurred sporadically in the Asia-Pacific region and have become a serious public health concern. It is hypothesized that virulent mutations in the EV-A71 genome cause these occasional outbreaks. Analysis of EV-A71 neurovirulence determinants is important, but there are no virulence determinants that are widely accepted among researchers. This is because most studies have been done in artificially infected mouse models and because EV-A71 mutates very quickly to adapt to the artificial host environment. Although EV-A71 uses multiple receptors for infection, it is clear that adaptation-related mutations alter the binding specificity of the receptors and allow the virus to adopt the best entry route for each environment. Such mutations have confused interpretations of virulence in animal models. This article will discuss how environment-adapted mutations in EV-A71 occur, how they affect virulence, and how such mutations can be avoided. We also discuss future perspectives for EV-A71 virulence research.

scholarly journals Molecular epidemiology of an enterovirus A71 outbreak associated with severe neurological disease, Spain, 2016

2019 ◽  
Vol 24 (7) ◽  
Author(s):  
Rubén González-Sanz ◽  
Didac Casas-Alba ◽  
Cristian Launes ◽  
Carmen Muñoz-Almagro ◽  
María Montserrat Ruiz-García ◽  
...  
Keyword(s):  
Neurological Diseases ◽  
Phylogenetic Analyses ◽  
Clinical Manifestations ◽  
Foot And Mouth Disease ◽  
Neurological Complications ◽  
Asia Pacific ◽  
Enterovirus A71 ◽  
Hospitalised Patients ◽  
Wide Range ◽  
Large Outbreak

Introduction Enterovirus A71 (EV-A71) is an emerging pathogen that causes a wide range of disorders including severe neurological manifestations. In the past 20 years, this virus has been associated with large outbreaks of hand, foot and mouth disease with neurological complications in the Asia-Pacific region, while in Europe mainly sporadic cases have been reported. In spring 2016, however, an EV-A71 outbreak associated with severe neurological cases was reported in Catalonia and spread further to other Spanish regions. Aim Our objective was to investigate the epidemiology and clinical characteristics of the outbreak. Methods We carried out a retrospective study which included 233 EV-A71-positive samples collected during 2016 from hospitalised patients. We analysed the clinical manifestations associated with EV-A71 infections and performed phylogenetic analyses of the 3’-VP1 and 3Dpol regions from all Spanish strains and a set of EV-A71 from other countries. Results Most EV-A71 infections were reported in children (mean age: 2.6 years) and the highest incidence was between May and July 2016 (83%). Most isolates (218/233) were classified as subgenogroup C1 and 217 of them were grouped in one cluster phylogenetically related to a new recombinant variant strain associated with severe neurological diseases in Germany and France in 2015 and 2016. Moreover, we found a clear association of EV-A71-C1 infection with severe neurological disorders, brainstem encephalitis being the most commonly reported. Conclusion An emerging recombinant variant of EV-A71-C1 was responsible for the large outbreak in 2016 in Spain that was associated with many severe neurological cases.

Virulence of enterovirus-A71 fluctuates depending on the phylogenetic clade formed in the epidemic year and epidemic region

2021 ◽  
Author(s):  
Kyousuke Kobayashi ◽  
Hidekazu Nishimura ◽  
Katsumi Mizuta ◽  
Tomoha Nishizawa ◽  
Son T. Chu ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Foot And Mouth Disease ◽  
Virus Genome ◽  
Mouth Disease ◽  
Asia Pacific ◽  
Enterovirus A71 ◽  
Viral Virulence ◽  
Foot And Mouth ◽  
Potential Risks ◽  
A Minor

Although epidemics of hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) have occurred worldwide, the Asia-Pacific region has seen large sporadic outbreaks with many severe neurological cases. This suggests that the virulence of the circulating viruses fluctuates in each epidemic and that HFMD outbreaks with many severe cases occur when highly virulent viruses are circulating predominantly, which has not been experimentally verified. Here, we analyzed 32 clinically isolated strains obtained in Japan from 2002 to 2013, along with 27 Vietnamese strains obtained from 2015 to 2016 that we characterized previously using human SCARB2 transgenic mice. Phylogenetic analysis of the P1 region classified them into five clades belonging to subgenogroup B5 (B5-I to B5-V) and five clades belonging to subgenogroup C4 (C4-I to C4-V) according to the epidemic year and region. Interestingly, the clade B5-I and B5-II were very virulent, while clades B5-III, B5-IV, and B5-V were less virulent. Clades C4-II, C4-III, C4-IV, and C4-V were virulent, while clade C4-I was not. The result experimentally showed for the first time that several clades with different virulence levels emerged one after another. The experimental virulence evaluation of circulating viruses using SCARB2 transgenic mice is helpful to assess potential risks of circulating viruses. These results also suggest that a minor nucleotide or amino acid substitution in the EV-A71 genome during circulation may cause fluctuations in virulence. The data presented herein may increase our understanding of the dynamics of viral virulence during epidemics. IMPORTANCE Outbreaks of hand, foot, and mouth disease (HFMD) with severe enterovirus A71 (EV-A71) cases have occurred repeatedly, mainly in Asia. In severe cases, central nervous system complications can lead to death, making it an infectious disease of importance to public health. An unanswered question about this disease is why outbreaks of HFMD with many severe cases sometimes occur. Here, we collected EV-A71 strains that were prevalent in Japan and Vietnam over the past 20 years and evaluated their virulence in a mouse model of EV-A71 infection. This method clearly revealed that viruses belonging to different clades have different virulence, indicating that the method is powerful to assess the potential risks of the circulating viruses. The results also suggested that factors in the virus genome may potentially cause an outbreak with many severe cases and that further studies may facilitate the prediction of large epidemics of EV-A71 in the future.

scholarly journals Phylogenetic Analysis of Enterovirus 71 Strains Isolated during Linked Epidemics in Malaysia, Singapore, and Western Australia

2001 ◽  
Vol 75 (16) ◽  
pp. 7732-7738 ◽  
Author(s):  
Peter McMinn ◽  
Katie Lindsay ◽  
David Perera ◽  
Hung Ming Chan ◽  
Kwai Peng Chan ◽  
...  
Keyword(s):  
Western Australia ◽  
Enterovirus 71 ◽  
Case Fatality ◽  
Foot And Mouth Disease ◽  
Severe Form ◽  
Asia Pacific ◽  
Pacific Region ◽  
Asia Pacific Region ◽  
Neurological Sequelae ◽  
Genetic Lineages

ABSTRACT Enterovirus 71 (EV71) is a frequent cause of hand, foot, and mouth disease (HFMD) epidemics associated with severe neurological sequelae in a small proportion of cases. There has been a significant increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997. Recent HFMD epidemics in this region have been associated with a severe form of brainstem encephalitis associated with pulmonary edema and high case fatality rates. In this study, we show that four genetic lineages of EV71 have been prevalent in the Asia-Pacific region since 1997, including two previously undescribed genogroups (B3 and B4). Furthermore, we show that viruses belonging to genogroups B3 and B4 have circulated endemically in Southeast Asia during this period and have been the primary cause of several large HFMD or encephalitis epidemics in Malaysia, Singapore, and Western Australia.

scholarly journals Lipidomic Profiling Reveals Significant Perturbations of Intracellular Lipid Homeostasis in Enterovirus-Infected Cells

2019 ◽  
Vol 20 (23) ◽  
pp. 5952 ◽  
Author(s):  
Bingpeng Yan ◽  
Zijiao Zou ◽  
Hin Chu ◽  
Gabriella Chan ◽  
Jessica Oi-Ling Tsang ◽  
...  
Keyword(s):  
Lipid Profile ◽  
Virus Replication ◽  
High Performance ◽  
Foot And Mouth Disease ◽  
Docosapentaenoic Acid ◽  
Enterovirus Infection ◽  
Flight Mass Spectrometry ◽  
Enterovirus A71 ◽  
Exogenous Addition ◽  
Life Threatening

Enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) are the most common causes of hand, foot, and mouth disease. Severe EV-A71 and CV-A16 infections may be associated with life-threatening complications. However, the pathogenic mechanisms underlying these severe clinical and pathological features remain incompletely understood. Lipids are known to play critical roles in multiple stages of the virus replication cycle. The specific lipid profile induced upon virus infection is required for optimal virus replication. The perturbations in the host cell lipidomic profiles upon enterovirus infection have not been fully characterized. To this end, we performed ultra-high performance liquid chromatography–electrospray ionization–quadrupole–time of flight-mass spectrometry (UPLC-ESI-Q-TOF-MS)-based lipidomics to characterize the change in host lipidome upon EV-A71 and CV-A16 infections. Our results revealed that 47 lipids within 11 lipid classes were significantly perturbed after EV-A71 and CV-A16 infection. Four polyunsaturated fatty acids (PUFAs), namely, arachidonic acid (AA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and eicosapentaenoic acid (EPA), were consistently upregulated upon EV-A71 and CV-A16 infection. Importantly, exogenously supplying three of these four PUFAs, including AA, DHA, and EPA, in cell cultures significantly reduced EV-A71 and CV-A16 replication. Taken together, our results suggested that enteroviruses might specifically modulate the host lipid pathways for optimal virus replication. Excessive exogenous addition of lipids that disrupted this delicate homeostatic state could prevent efficient viral replication. Precise manipulation of the host lipid profile might be a potential host-targeting antiviral strategy for enterovirus infection.

scholarly journals A tool for rapid assessment of wildlife markets in the Asia-Pacific Region for risk of future zoonotic disease outbreaks

One Health ◽  
2021 ◽  
pp. 100279
Author(s):  
Eric Wikramanayake ◽  
Dirk U. Pfeiffer ◽  
Ioannis Magouras ◽  
Anne Conan ◽  
Stefan Ziegler ◽  
...  
Keyword(s):  
Rapid Assessment ◽  
Disease Outbreaks ◽  
Zoonotic Disease ◽  
Asia Pacific ◽  
Pacific Region ◽  
Asia Pacific Region

scholarly journals Dysregulated autophagy contributes to the pathogenesis of enterovirus A71 infection

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chuanjie Zhang ◽  
Yawei Li ◽  
Jingfeng Li
Keyword(s):  
Foot And Mouth Disease ◽  
Epidemiological Studies ◽  
Asia Pacific ◽  
Global Public Health ◽  
Viral Spread ◽  
Autophagy Induction ◽  
Viral Therapy ◽  
Enterovirus A71 ◽  
Promising Therapeutic Target ◽  
Fundamental Research

AbstractEnterovirus A71 (EVA71) infection continues to remain a vital threat to global public health, especially in the Asia–Pacific region. It is one of the most predominant pathogens that cause hand, foot, and mouth disease (HFMD), which occurs mainly in children below 5 years old. Although EVA71 prevalence has decreased sharply in China with the use of vaccines, epidemiological studies still indicate that EVA71 infection involves severe and even fatal HFMD cases. As a result, it remains more fundamental research into the pathogenesis of EVA71 as well as to develop specific anti-viral therapy. Autophagy is a conserved, self-degradation system that is critical for maintaining cellular homeostasis. It involves a variety of biological functions, such as development, cellular differentiation, nutritional starvation, and defense against pathogens. However, accumulating evidence has indicated that EVA71 induces autophagy and hijacks the process of autophagy for their optimal infection during the different stages of life cycle. This review provides a perspective on the emerging evidence that the “positive feedback” between autophagy induction and EVA71 infection, as well as its potential mechanisms. Furthermore, autophagy may be involved in EVA71-induced nervous system impairment through mediating intracranial viral spread and dysregulating host regulator involved self-damage. Autophagy is a promising therapeutic target in EVA71 infection.

scholarly journals Susceptibility and cytokine responses of human neuronal cells to multiple circulating EV-A71 genotypes in India

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Madhu Chhanda Mohanty ◽  
Swapnil Yashavant Varose ◽  
Vinay Kumar Saxena
Keyword(s):  
Inflammatory Cytokines ◽  
Neuronal Cells ◽  
Foot And Mouth Disease ◽  
Asia Pacific ◽  
Delayed Response ◽  
Cytokine Responses ◽  
Enterovirus A71 ◽  
Infected Cells ◽  
Human Neuronal Cells

AbstractEnterovirus-A71 (EV-A71) associated Hand, foot and mouth disease (HFMD) is a highly contagious viral infection affecting children in Asia–Pacific region and has become a major threat to public health. Although several EV-A71 genotypes (C, D, and G) were isolated in India in recent years, no recognizable outbreak of EV-A71 caused HFMD, Acute Flaccid paralysis (AFP) or encephalitis have been reported so far. It is essential to study the pathogenicity or cell tropism of these Indian isolates in order to understand their tendency to cause disease. We investigated the susceptibility and cytokine responses of indigenous EV-A71 genotypes (D and G) isolated from cases of AFP and genotype C viruses isolated from cases of HFMD and encephalitis, in human cells in-vitro. Although all three EV-A71 genotypes could infect and replicate in human muscle and neuronal cells, the genotype D virus showed a delayed response in human neuronal cells. Quantification of cytokine secretion in response to these isolates followed by confirmation with gene expression assays in human neuronal cells revealed significantly higher secretion of pro-inflammatory cytokines TNF-α IL-8, IL-6, IP-10 (p < 0.001) in G genotype infected cells as compared to pathogenic C genotypes whereas the genotype D virus could not induce any of the inflammatory cytokines. These findings will help to better understand the host response to indigenous EV-A71 genotypes for management of future EV-A71 outbreaks in India, if any.

scholarly journals The History of Enterovirus A71 Outbreaks and Molecular Epidemiology in the Asia-Pacific Region

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Jiratchaya Puenpa ◽  
Nasamon Wanlapakorn ◽  
Sompong Vongpunsawad ◽  
Yong Poovorawan
Keyword(s):  
Vaccine Development ◽  
Epidemiological Data ◽  
Healthcare Services ◽  
Developed Countries ◽  
Asia Pacific ◽  
Diagnostic Tools ◽  
Future Research ◽  
Pacific Region ◽  
Asia Pacific Region ◽  
Enterovirus A71

Abstract Enterovirus A71 (EV-A71) is one of the common causative pathogens for hand foot and mouth disease (HFMD) affecting young children. HFMD outbreak can result in a substantial pediatric hospitalization and burden the healthcare services, especially in less-developed countries. Since the initial epidemic of predominantly EV-A71 in California in 1969, the high prevalence of HFMD in the Asia-pacific region and elsewhere around the world represents a significant morbidity in this age group. With the advent of rapid and accurate diagnostic tools, there has been a dramatic increase in the number of laboratory-confirmed EV-A71 infection over the past two decades. The population, cultural, and socioeconomic diversity among countries in the Asia-Pacific region all influence the transmission and morbidity associated with HFMD. This review summarizes the current state of epidemiology of EV-A71 in Asia-Pacific countries based on the most recent epidemiological data and available information on the prevalence and disease burden. This knowledge is important in guiding the prevention, control and future research on vaccine development of this highly contagious disease of significant socioeconomic implications in public health.

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