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Stability of enteroviruses on toys commonly found in kindergarten

Baharin SNAN, Tan SL, Sam IC, Chan YF

Trop Biomed, 2023 Dec 01;40(4):478-485.
PMID: 38308836 DOI: 10.47665/tb.40.4.014

Hand, foot, and mouth disease (HFMD) is a contagious childhood disease caused by enteroviruses including enterovirus A71 (EV-A71), coxsackievirus A6 (CV-A6) and CV-A16 transmitted via direct and indirect contact. Different types of toy surfaces can affect the stability of viruses. Understanding the stability of enteroviruses on toys provides insightful data for effective disinfection in kindergartens or homes. Porous (ethylene-vinyl acetate mat foam, paper, pinewood, polyester fabric, and squishy polyurethane foam) and non-porous (acrylonitrile butadiene styrene plastic and stainless-steel coin) surfaces were inoculated with EV-A71 at 4, 24, and 35°C, and coxsackieviruses at 24°C. Infectious enteroviruses were recovered and titred in median tissue culture infectious dose assay (TCID50). Atomic force microscopy (AFM) images were taken from surfaces to examine association of surface roughness with virus stability. Overall, infectious enteroviruses were persistent on all non-porous and porous surfaces. Virus persistence was longest at 4°C followed by 24°C and 35°C. EV-A71 half-lives ranged between 6.4-12.8 hours at 4°C, 2.4-6.7 hours at 24°C, and 0.13-2.7 hours at 35°C. At lower virus titres exposed to 24°C, half-lives of enteroviruses ranged from 0.1-1.4 hours. Surface roughness values from AFM suggested smooth surfaces of non-porous surfaces were associated with better virus stability. Temperature, enterovirus concentration, and type of surface affected persistence and stability of enteroviruses. Our findings suggest both porous and non-porous surfaces in kindergartens allow enterovirus persistence and should be frequently disinfected to curb HFMD outbreaks in kindergartens.

Matched MeSH terms: Enterovirus*; Enterovirus A, Human*
Vaccine candidates generated by codon and codon pair deoptimization of enterovirus A71 protect against lethal challenge in mice

Lee MHP, Tan CW, Tee HK, Ong KC, Sam IC, Chan YF

Vaccine, 2021 03 19;39(12):1708-1720.
PMID: 33640144 DOI: 10.1016/j.vaccine.2021.02.024

Enterovirus A71 (EV-A71) causes hand, foot and mouth disease (HFMD) in young children. It is associated with severe neurological complications and death. This study aims to develop a live-attenuated vaccine by codon deoptimization (CD) and codon-pair deoptimization (CPD) of EV-A71. CD is generated by introducing the least preferred codons for amino acids while CPD increases the presence of underrepresented codon pairs in the specific genes. CD and CPD chimeras were generated by synonymous mutations at the VP2, VP3, VP1 and 2A gene regions, designated as XYZ. All twelve deoptimized viruses were viable with similar replication kinetics, but the plaque sizes were inversely proportional to the level of deoptimization. All the deoptimized viruses showed attenuated growth in vitro with reduced viral protein expression at 48 h and lower viral RNA at 39 °C. Six-week-old ICR mice were immunized intraperitoneally with selected CD and CPD X and XY vaccine candidates covering the VP2-VP3 and VP2-VP3-VP1 genes, respectively. All vaccine candidates elicited high anti-EV-A71 IgG levels similar to wild-type (WT) EV-A71. The CD X and CPD X vaccines produced robust neutralizing antibodies but not the CD XY and CPD XY. On lethal challenge, offspring of mice immunized with WT, CD X and CPD X were fully protected, but the CD XY- and CPD XY-vaccinated mice had delayed symptoms and eventually died. Similarly, active immunization of 1-day-old suckling mice with CD X, CPD X and CD XY vaccine candidates provided complete immune protection but CPD XY only protected 40% of the challenged mice. Histology of the muscles from CD X- and CPD X-vaccinated mice showed minimal pathology compared to extensive inflammation in the post-challenged mock-vaccinated mice. Overall, we demonstrated that the CD X and CPD X elicited good neutralizing antibodies, conferred immune protection and are promising live-attenuated vaccine candidates for EV-A71.

Matched MeSH terms: Enterovirus*
Impact of genetic changes, pathogenicity and antigenicity on Enterovirus- A71 vaccine development

Yee PTI, Laa Poh C

Virology, 2017 06;506:121-129.
PMID: 28384566 DOI: 10.1016/j.virol.2017.03.017

Enterovirus-A71 (EV-A71) is an etiological agent of the hand, foot and mouth disease (HFMD). EV-A71 infection produces high fever and ulcers in children. Some EV-A71 strains produce severe infections leading to pulmonary edema and death. Although the protective efficacy of the inactivated vaccine (IV) was ≥90% against mild HFMD, there was approximately 80% protection against severe HFMD. The monovalent EV-A71 IV elicits humoral immunity but lacks long-term immunogenicity. Spontaneous mutations of the EV-A71 genome could lead to antigenicity changes and the virus may not be neutralized by antibodies elicited by the IV. A better alternative would be the live attenuated vaccine (LAV) that elicits cellular and humoral immunity. The LAV induces excellent antigenicity and chances of reversion is reduced by presence of multiple mutations which could reduce pathogenicity. Besides CV-A16, outbreaks have been caused by CV-A6 and CV-A10, hence the development of bivalent and trivalent vaccines is required.

Matched MeSH terms: Enterovirus Infections/immunology; Enterovirus Infections/prevention & control*; Enterovirus Infections/virology; Enterovirus/genetics*; Enterovirus/immunology; Enterovirus/pathogenicity*
Hand, Foot, and Mouth Disease: A Narrative Review

Leung AKC, Lam JM, Barankin B, Leong KF, Hon KL

Recent Adv Inflamm Allergy Drug Discov, 2022;16(2):77-95.
PMID: 36284392 DOI: 10.2174/1570180820666221024095837

BACKGROUND: Hand, foot, and mouth disease is a common viral disease in childhood. Because the disease has the potential to reach epidemic levels and mortality is high in some countries, early recognition of this disease is of paramount importance.
OBJECTIVE: This purpose of this article is to familiarize pediatricians with the clinical manifestations and management of hand, foot, and mouth disease.
METHODS: A search was conducted in February 2022 in PubMed Clinical Queries using the key term "hand, foot, and mouth disease". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in English were included in this review.
RESULTS: Hand, foot, and mouth disease is characterized by a painful oral enanthem and asymptomatic exanthem on the palms and soles. Children younger than 5 years are most commonly affected. Hand, foot, and mouth disease caused by enterovirus A71 is more severe and has a higher rate of complications than that attributed to other viruses such as coxsackievirus A16. Circulatory failure secondary to myocardial impairment and neurogenic pulmonary edema secondary to brainstem damage are the main causes of death. Fortunately, the disease is usually benign and resolves in 7 to10 days without sequelae. Given the self-limited nature of most cases, treatment is mainly symptomatic and supportive. Intravenous immunoglobulin should be considered for the treatment of severe/complicated hand, foot, and mouth disease and has been recommended by several national and international guideline committees. Currently, there are no specific antiviral agents approved for the treatment of the disease. Drugs such as ribavirin, suramin, mulberroside C, aminothiazole analogs, and sertraline have emerged as potential candidates for the treatment of hand, foot, and mouth disease. Vaccination of susceptible individuals in high-risk areas and good personal hygiene are important preventative measures to combat the disease.
CONCLUSION: Familiarity of the disease including its atypical manifestations is crucial so that a correct diagnosis can be made, and appropriate treatment initiated. A timely diagnosis can help avoid contact with the affected individual and decrease the risk of an outbreak.

Matched MeSH terms: Enterovirus*
Fulltext Spatio-temporal analysis on enterovirus cases through integrated surveillance in Taiwan

Chan TC, Hwang JS, Chen RH, King CC, Chiang PH

BMC Public Health, 2014 Jan 08;14:11.
PMID: 24400725 DOI: 10.1186/1471-2458-14-11

BACKGROUND: Severe epidemics of enterovirus have occurred frequently in Malaysia, Singapore, Taiwan, Cambodia, and China, involving cases of pulmonary edema, hemorrhage and encephalitis, and an effective vaccine has not been available. The specific aim of this study was to understand the epidemiological characteristics of mild and severe enterovirus cases through integrated surveillance data.
METHODS: All enterovirus cases in Taiwan over almost ten years from three main databases, including national notifiable diseases surveillance, sentinel physician surveillance and laboratory surveillance programs from July 1, 1999 to December 31, 2008 were analyzed. The Pearson's correlation coefficient was applied for measuring the consistency of the trends in the cases between different surveillance systems. Cross correlation analysis in a time series model was applied for examining the capability to predict severe enterovirus infections. Poisson temporal, spatial and space-time scan statistics were used for identifying the most likely clusters of severe enterovirus outbreaks. The directional distribution method with two standard deviations of ellipse was applied to measure the size and the movement of the epidemic.
RESULTS: The secular trend showed that the number of severe EV cases peaked in 2008, and the number of mild EV cases was significantly correlated with that of severe ones occurring in the same week [r = 0.553, p

Matched MeSH terms: Enterovirus Infections/epidemiology*; Enterovirus Infections/prevention & control; Enterovirus Infections/virology; Enterovirus; Enterovirus A, Human/isolation & purification*
[Myocarditis caused by enteroviruses in Greece--and in Germany?]

Braun R, Hassler D, Kimmig P

Dtsch. Med. Wochenschr., 2002 Jun 21;127(25-26):1364.
PMID: 12136792
Matched MeSH terms: Enterovirus Infections/diagnosis; Enterovirus Infections/epidemiology*; Enterovirus Infections/therapy; Enterovirus Infections/virology; Enterovirus/classification
Enterovirus 71: the virus, its infections and outbreaks

Ho M

J Microbiol Immunol Infect, 2000 Dec;33(4):205-16.
PMID: 11269363

Enterovirus 71 (EV71) was first recognized in 1974. Since then it has been implicated in 13 small and large outbreaks world-wide. Large outbreaks of hand, foot and mouth disease (HFMD), mostly benign, occurred in Japan in 1973 and 1978. Four outbreaks with brain stem encephalitis and significant numbers of deaths occurred in Bulgaria and Hungary in the late 1970's and in Malaysia and Taiwan in 1997 and 1998 respectively. During the latter two epidemics, pulmonary edema and hemorrhage often leading to quick deaths in children aged from 0.5 to 3 years old was first recognized. In Taiwan 78 deaths and over 100,000 cases of HFMD occurred. Coxsackie A16 cocirculated with EV 71, without however, causing any severe illnesses. The transmission of EV 71 was related to number of siblings in a household, rural residence and contact with cases of HFMD. Genotype analyses show that genotypes have changed with time in the United States and Japan. Recent isolates from Japan are similar to the isolates from Malaysia and Taiwan in 1997 and 1998, respectively. Even though genotype analysis has not identified specific sequences responsible for neurovirulence, the strains causing brain stem encephalitis and pulmonary edema in the Far East are similar and have arisen since 1997. Seroepidemiological studies in Taiwan suggest that children aged from 0.5 to 4 years old are most susceptible while the rest of the population are over 50% immune. Theoretically there is a pool of such susceptible subjects every few years. In prevention for another major outbreak, a simple, inactivated Salk type vaccine should be immediately prepared and made available.

Matched MeSH terms: Enterovirus Infections/complications*; Enterovirus Infections/epidemiology; Enterovirus Infections/virology; Enterovirus/classification*; Enterovirus/genetics
Fulltext Outbreaks of enterovirus 71 infection

AbuBakar S, Chan YF, Lam SK

N Engl J Med, 2000 Feb 3;342(5):355-6.
PMID: 10660400 DOI: 10.1056/NEJM200002033420513
Matched MeSH terms: Enterovirus Infections/epidemiology*; Enterovirus Infections/virology; Enterovirus/classification*; Enterovirus/genetics; Enterovirus/isolation & purification
Fulltext Characterization of Plaque Variants and the Involvement of Quasi-Species in a Population of EV-A71

Mandary MB, Masomian M, Ong SK, Poh CL

Viruses, 2020 Jun 17;12(6).
PMID: 32560288 DOI: 10.3390/v12060651

Viral plaque morphologies in human cell lines are markers for growth capability and they have been used to assess the viral fitness and selection of attenuated mutants for live-attenuated vaccine development. In this study, we investigate whether the naturally occurring plaque size variation reflects the virulence of the variants of EV-A71. Variants of two different plaque sizes (big and small) from EV-A71 sub-genotype B4 strain 41 were characterized. The plaque variants displayed different in vitro growth kinetics compared to the parental wild type. The plaque variants showed specific mutations being present in each variant strain. The big plaque variants showed four mutations I97L, N104S, S246P and N282D in the VP1 while the small plaque variants showed I97T, N237T and T292A in the VP1. No other mutations were detected in the whole genome of the two variants. The variants showed stable homogenous small plaques and big plaques, respectively, when re-infected in rhabdomyosarcoma (RD) and Vero cells. The parental strain showed faster growth kinetics and had higher viral RNA copy number than both the big and small plaque variants. Homology modelling shows that both plaque variants have differences in the structure of the VP1 protein due to the presence of unique spontaneous mutations found in each plaque variant This study suggests that the EV-A71 sub-genotype B4 strain 41 has at least two variants with different plaque morphologies. These differences were likely due to the presence of spontaneous mutations that are unique to each of the plaque variants. The ability to maintain the respective plaque morphology upon passaging indicates the presence of quasi-species in the parental population.

Matched MeSH terms: Enterovirus Infections/virology*; Enterovirus A, Human/classification; Enterovirus A, Human/genetics*; Enterovirus A, Human/isolation & purification; Enterovirus A, Human/pathogenicity
[Enterovirus type 70, a pathogenic agent of acute haemorrhagic conjunctivitis (author's transl)]

Kopecká D

Cesk Epidemiol Mikrobiol Imunol, 1977 Nov;25(6):342-4.
PMID: 188556
Matched MeSH terms: Enterovirus Infections/epidemiology*; Enterovirus/isolation & purification
Fulltext T Cell Immunity To Enterovirus 71 Infection In Humans And Implications For Vaccine Development

Yee PTI, Poh CL

Int J Med Sci, 2018;15(11):1143-1152.
PMID: 30123051 DOI: 10.7150/ijms.26450

Enterovirus 71 (EV-A71) is one of the major pathogens causing hand, foot and mouth disease (HFMD). Some strains can lead to neurological disease and fatality in children. Up to date, there is no FDA-approved vaccine to prevent severe HFMD and mortality. Although the inactivated vaccine has advanced to production in China, lack of long-term protection and the requirement of multiple boosters have necessitated the development of other types of vaccines. Recent studies indicate that cellular and not humoral immunity determines the clinical outcome of EV-A71 infections. High levels of cytokines such as IL-1β, IL-6, IL-10 and IFN-γ tend to correlate with clinical severity in patients with pulmonary edema and encephalitis. The live attenuated vaccine may serve as the preferred choice as it can induce excellent humoral and cellular immunity as well as live-long immunity. Expression of certain HLA alleles such as TNF-α promoter type II (-308 allele), HLA-A33 and HLA-DR17 responses have been linked to severe HFMD. However, the high variability of MHC genes could restrict T cell recognition and be a major obstacle in the design of peptide vaccines. Hence, the development of a T cell universal vaccine (incorporating both CD4+ and CD8+ T cell epitopes) that induces broad, multifunctional and cross-reactive CD8+ T cell responses maybe desirable.

Matched MeSH terms: Enterovirus Infections/immunology*; Enterovirus A, Human/immunology*
Fulltext Recent developments in antiviral agents against enterovirus 71 infection

Tan CW, Lai JK, Sam IC, Chan YF

J Biomed Sci, 2014;21:14.
PMID: 24521134 DOI: 10.1186/1423-0127-21-14

Enterovirus 71 (EV-71) is the main etiological agent of hand, foot and mouth disease (HFMD). Recent EV-71 outbreaks in Asia-Pacific were not limited to mild HFMD, but were associated with severe neurological complications such as aseptic meningitis and brainstem encephalitis, which may lead to cardiopulmonary failure and death. The absence of licensed therapeutics for clinical use has intensified research into anti-EV-71 development. This review highlights the potential antiviral agents targeting EV-71 attachment, entry, uncoating, translation, polyprotein processing, virus-induced formation of membranous RNA replication complexes, and RNA-dependent RNA polymerase. The strategies for antiviral development include target-based synthetic compounds, anti-rhinovirus and poliovirus libraries screening, and natural compound libraries screening. Growing knowledge of the EV-71 life cycle will lead to successful development of antivirals. The continued effort to develop antiviral agents for treatment is crucial in the absence of a vaccine. The coupling of antivirals with an effective vaccine will accelerate eradication of the disease.

Matched MeSH terms: Enterovirus Infections/drug therapy*; Enterovirus Infections/genetics; Enterovirus Infections/pathology; Enterovirus A, Human/drug effects*; Enterovirus A, Human/genetics*; Enterovirus A, Human/pathogenicity
Fulltext Enterovirus 71 outbreak, Brunei

AbuBakar S, Sam IC, Yusof J, Lim MK, Misbah S, MatRahim N, et al.

Emerg Infect Dis, 2009 Jan;15(1):79-82.
PMID: 19116058 DOI: 10.3201/eid1501.080264

Enterovirus 71 (EV71) outbreaks occur periodically in the Asia-Pacific region. In 2006, Brunei reported its first major outbreak of EV71 infections, associated with fatalities from neurologic complications. Isolated EV71 strains formed a distinct lineage with low diversity within subgenogroup B5, suggesting recent introduction and rapid spread within Brunei.

Matched MeSH terms: Enterovirus Infections/mortality; Enterovirus Infections/epidemiology*; Enterovirus Infections/virology; Enterovirus A, Human/classification; Enterovirus A, Human/genetics; Enterovirus A, Human/isolation & purification*
A review on current diagnostic tools and potential optical absorption spectroscopy for HFMD detection

Mustafa FH, Ismail I, Ahmad Munawar AAZ, Abdul Basir B, Shueb RH, Irekeola AA, et al.

Anal Biochem, 2023 Dec 15;683:115368.
PMID: 37890549 DOI: 10.1016/j.ab.2023.115368

Hand, Foot, and Mouth Disease (HFMD) is an outbreak infectious disease that can easily spread among children under the age of five. The most common causative agents of HFMD are enterovirus 71 (EV71) and coxsackievirus A16 (CVA16), but infection caused by EV71 is more associated with fatalities due to severe neurological disorders. The present diagnosis methods rely on physical examinations by the doctors and further confirmation by laboratories detection methods such as viral culture and polymerase chain reaction. Clinical signs of HFMD infection and other childhood diseases such as chicken pox, and allergies are similar, yet the genetics and pathogenicity of the viruses are substantially different. Thus, there is an urgent need for an early screening of HFMD using an inexpensive and user-friendly device that can directly detect the causative agents of the disease. This paper reviews current HFMD diagnostic methods based on various target types, such as nucleic acid, protein, and whole virus. This was followed by a thorough discussion on the emerging sensing technologies for HFMD detection, including surface plasmon resonance, electrochemical sensor, and surface enhanced Raman spectroscopy. Lastly, optical absorption spectroscopic method was critically discussed and proposed as a promising technology for HFMD screening and detection.

Matched MeSH terms: Enterovirus A, Human*
Detection of enteroviruses from clinical specimens

Poh CL, Tan EL

Methods Mol Biol, 2011;665:65-77.
PMID: 21116796 DOI: 10.1007/978-1-60761-817-1_5

Enteroviruses are positive stranded RNA viruses belonging to the genus Enterovirus of the Picornaviridae family. Human enteroviruses are transmitted through the fecal-oral route and have been shown to cause mild to life-threatening diseases. Various diagnostic methods have been developed to detect enteroviruses from clinical specimens but many were impeded by requirements for special reagents, lengthy procedures, low sensitivity or cross-reactivity. This chapter describes rapid and highly sensitive methods of enteroviral detection directly from clinical specimens based on a conventional one-step Reverse Transcription polymerase chain reaction (RT-PCR) and a one-step real-time RT-PCR.

Matched MeSH terms: Enterovirus Infections/diagnosis*; Enterovirus/classification; Enterovirus/genetics; Enterovirus/isolation & purification*
Understanding Enterovirus 71 Neuropathogenesis and Its Impact on Other Neurotropic Enteroviruses

Ong KC, Wong KT

Brain Pathol, 2015 Sep;25(5):614-24.
PMID: 26276025 DOI: 10.1111/bpa.12279

Enterovirus A71 (EV-A71) belongs to the species group A in the Enterovirus genus within the Picornaviridae family. EV-A71 usually causes self-limiting hand, foot and mouth disease or herpangina but rarely causes severe neurological complications such as acute flaccid paralysis and encephalomyelitis. The pathology and neuropathogenesis of these neurological syndromes is beginning to be understood. EV-A71 neurotropism for motor neurons in the spinal cord and brainstem, and other neurons, is mainly responsible for central nervous system damage. This review on the general aspects, recent developments and advances of EV-A71 infection will focus on neuropathogenesis and its implications on other neurotropic enteroviruses, such as poliovirus and the newly emergent Enterovirus D68. With the imminent eradication of poliovirus, EV-A71 is likely to replace it as an important neurotropic enterovirus of worldwide importance.

Matched MeSH terms: Enterovirus Infections/pathology*; Enterovirus A, Human/pathogenicity*; Enterovirus D, Human/pathogenicity
Fulltext Enterovirus type 70: the etiologic agent of pandemic acute haemorrhagic conjunctivitis

Mirkovic RR, Kono R, Yin-Murphy M, Sohier R, Schmidt NJ, Melnick JL

Bull World Health Organ, 1973;49(4):341-6.
PMID: 4368683

A new enterovirus, now classified as enterovirus type 70, was isolated from the conjunctiva of patients with acute haemorrhagic conjunctivitis during the 1971 epidemics that occurred in Japan, Singapore, and Morocco. These epidemics were parts of a pandemic involving Africa (Algeria, Ghana, Morocco, Nigeria, and Tunisia), Asia (Cambodia, China (Province of Taiwan), Hong Kong, India, Indonesia, Japan, Malaysia, the Philippines, Singapore, and Thailand), and England during 1969-71. A representative strain from each of the three epidemic areas was studied cooperatively. The strains exhibited the physicochemical characteristics of enteroviruses. Cross-neutralization tests showed that these viruses were distinct from all known human enterovirus immunotypes, but that they were antigenically closely related. The human origin of the viruses was demonstrated by the appearance of homologous neutralizing antibodies during convalescence in patients with acute haemorrhagic conjunctivitis.

Matched MeSH terms: Enterovirus Infections/microbiology*; Enterovirus Infections/epidemiology; Enterovirus/classification; Enterovirus/isolation & purification*
Fulltext Isolation and Identification of Inter-Species Enterovirus Recombinant Genomes

Bentley K, Tee HK, Pearson A, Lowry K, Waugh S, Jones S, et al.

Viruses, 2021 11 29;13(12).
PMID: 34960659 DOI: 10.3390/v13122390

Positive-strand RNA virus evolution is partly attributed to the process of recombination. Although common between closely genetically related viruses, such as within species of the Enterovirus genus of the Picornaviridae family, inter-species recombination is rarely observed in nature. Recent studies have shown recombination is a ubiquitous process, resulting in a wide range of recombinant genomes and progeny viruses. While not all recombinant genomes yield infectious progeny virus, their existence and continued evolution during replication have critical implications for the evolution of the virus population. In this study, we utilised an in vitro recombination assay to demonstrate inter-species recombination events between viruses from four enterovirus species, A-D. We show that inter-species recombinant genomes are generated in vitro with polymerase template-switching events occurring within the virus polyprotein coding region. However, these genomes did not yield infectious progeny virus. Analysis and attempted recovery of a constructed recombinant cDNA revealed a restriction in positive-strand but not negative-strand RNA synthesis, indicating a significant block in replication. This study demonstrates the propensity for inter-species recombination at the genome level but suggests that significant sequence plasticity would be required in order to overcome blocks in the virus life cycle and allow for the production of infectious viruses.

Matched MeSH terms: Enterovirus Infections/virology; Enterovirus/classification; Enterovirus/genetics*; Enterovirus/isolation & purification
Molecular epidemiology of human enterovirus 71 strains and recent outbreaks in the Asia-Pacific region: comparative analysis of the VP1 and VP4 genes

Cardosa MJ, Perera D, Brown BA, Cheon D, Chan HM, Chan KP, et al.

Emerg Infect Dis, 2003 Apr;9(4):461-8.
PMID: 12702227

This study provides a comprehensive overview of the molecular epidemiology of human enterovirus 71 (HEV71) in the Asia-Pacific region from 1997 through 2002. Phylogenetic analysis of the VP4 and VP1 genes of recent HEV71 strains indicates that several genogroups of the virus have been circulating in the Asia-Pacific region since 1997. The first of these recent outbreaks, described in Sarawak (Malaysian Borneo) in 1997, was caused by genogroup B3. This outbreak was followed by large outbreaks in Taiwan in 1998, caused by genogroup C2, and in Perth (Western Australia) in 1999, where viruses belonging to genogroups B3 and C2 cocirculated. Singapore, Taiwan, and Sarawak had HEV71 epidemics in 2000, caused predominantly by viruses belonging to genogroup B4; however, large numbers of fatalities were observed only in Taiwan. HEV71 was identified during an epidemic of hand, foot and mouth disease in Korea; that epidemic was found to be due to viruses constituting a new genogroup, C3.

Matched MeSH terms: Enterovirus Infections/epidemiology*; Enterovirus/genetics*; Enterovirus/isolation & purification; Enterovirus/pathogenicity
Fulltext Cell and tissue tropism of enterovirus 71 and other enteroviruses infections

Lin JY, Shih SR

J Biomed Sci, 2014;21:18.
PMID: 24602216 DOI: 10.1186/1423-0127-21-18

Enterovirus 71 (EV71) is a member of Picornaviridae that causes mild and self-limiting hand, foot, and mouth disease (HFMD). However, EV71 infections can progress to polio-like paralysis, neurogenic pulmonary edema, and fatal encephalitis in infants and young children. Large EV71 outbreaks have been reported in Taiwan, China, Japan, Malaysia, Singapore, and Australia. This virus is considered a critical emerging public health threat. EV71 is an important crucial neurotropic enterovirus for which there is currently no effective antiviral drug or vaccine. The mechanism by which EV71 causes severe central nervous system complications remains unclear. The interaction between the virus and the host is vital for viral replication, virulence, and pathogenicity. SCARB2 or PSGL-1 receptor binding is the first step in the development of viral infections, and viral factors (e.g., 5' UTR, VP1, 3C, 3D, 3' UTR), host factors and environments (e.g., ITAFs, type I IFN) are also involved in viral infections. The tissue tropism and pathogenesis of viruses are determined by a combination of several factors. This review article provides a summary of host and virus factors affecting cell and tissue tropism and the pathogenesis of enteroviruses.

Matched MeSH terms: Enterovirus Infections/genetics; Enterovirus Infections/epidemiology*; Enterovirus Infections/virology; Enterovirus A, Human/genetics; Enterovirus A, Human/pathogenicity*

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