Molecular epidemiology of enterovirus 71 infection in the Western Pacific Region

Shimizu, Hiroyuki; Utama, Andi; Onnimala, Napa; Li, Chen; Li-bi, Zhang; Ma, Yanhui; Pongsuwanna, Yaowapa; Miyamura, Tatsuo

doi:10.1046/j.1442-200x.2004.01868.x

Cited by 139 publications

(112 citation statements)

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“…EV71 was propagated and purified as described previously (8). Briefly, EV71 strain 1095 (23,24) was propagated in HeLa cells for 24 h. The media and cells were collected and processed by freezing and thawing three times. Cell debris was pelleted by centrifugation, and the supernatant was precipitated with polyethylene glycol (PEG) 8000.…”

Section: Methodsmentioning

confidence: 99%

A Strain-Specific Epitope of Enterovirus 71 Identified by Cryo-Electron Microscopy of the Complex with Fab from Neutralizing Antibody

Lee

Cifuente

Ashley

et al. 2013

J Virol

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e Enterovirus 71 (EV71) is a picornavirus that causes outbreaks of hand, foot, and mouth disease (HFMD), primarily in the Asia-Pacific area. Unlike coxsackievirus A16, which also causes HFMD, EV71 induces severe neuropathology leading to high fatalities, especially among children under the age of 6 years. Currently, no established vaccines or treatments are available against EV71 infection. The monoclonal antibody MA28-7 neutralizes only specific strains of EV71 that have a conserved glycine at amino acid VP1-145, a surface-exposed residue that maps to the 5-fold vertex and that has been implicated in receptor binding. The cryo-electron microscopy structure of a complex between EV71 and the Fab fragment of MA28-7 shows that only one Fab fragment occupies each 5-fold vertex. A positively charged patch, which has also been implicated in receptor binding, lies within the Fab footprint. We identify the strain-specific epitope of EV71 and discuss the possible neutralization mechanisms of the antibody. E nterovirus 71 (EV71) infection causes outbreaks of hand, foot, and mouth disease (HFMD), predominantly in the Asia-Pacific region (1, 2). Whereas most EV71 infections are self-limiting, neurological and systemic complications can develop that range from aseptic meningitis to encephalitis and acute flaccid paralysis. Infection can lead to lethal pulmonary edema and heart failure (2), with mortality being especially high in young children under the age of 6 (2, 3). As seasonal outbreaks of HFMD are recurring around the world, development of a vaccine and antiviral therapies for EV71 has become an urgent concern.A member of the Picornaviridae family, EV71 has a nonenveloped, icosahedral capsid comprised of 60 copies of each of four viral structural proteins (VP1 to VP4) (4). Recent studies have solved the structures for three strains of EV71 (MY104 [5], Fuyang [6], and 1095 [7]), demonstrating that EV71 has the general features of picornavirus capsids, including the 5-fold "mesa" and the depression around the mesa called the "canyon" (5-8). Conserved residues VP1-242K and VP1-244K form positively charged patches on the 5-fold mesa (6), and this symmetry-related clustering of positive charges has been suggested as a common mechanism for heparan sulfate binding in enteroviruses (9).Several cellular receptors for EV71 have been identified: scavenger receptor B2 (SCARB2), P-selectin glycoprotein ligand-1 (PSGL-1), and heparan sulfate (HS) (10-12). SCARB2, which is expressed on a broad variety of cell types, likely binds to the virus canyon and induces the transition of the virion that is required for uncoating (13-15). PSGL-1, which is expressed exclusively on lymphocytes, binds only specific EV71 strains and supports viral replication in lymphocytes in a PSGL-1-dependent manner (11). According to recent studies, PSGL-1 and HS bind the positively charged patches on the 5-fold mesa of EV71 and provide initial attachment on the cell (12,16,17). We recently found that the PSGL-1 binding phenotype of EV71 strains is regulated b...

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Section: Methodsmentioning

confidence: 99%

A Strain-Specific Epitope of Enterovirus 71 Identified by Cryo-Electron Microscopy of the Complex with Fab from Neutralizing Antibody

Lee

Cifuente

Ashley

et al. 2013

J Virol

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“…These symptoms were of neurogenic origin, and brain stem involvement (direct destruction of the vasomotor and respiratory centers) was critical (10,21,25,31,57). Disseminated infection of EV71 in the central nervous system (CNS) might in part explain the EV71-specific neuropathogenesis (40).Molecular epidemiological studies indicate that EV71 consists of at least 10 genotypes (A, B1 to -5, and C1 to -4) (7,26,33,37,49). The prototype BrCr strain is the sole member of genotype A (8).…”

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“…Molecular epidemiological studies indicate that EV71 consists of at least 10 genotypes (A, B1 to -5, and C1 to -4) (7,26,33,37,49). The prototype BrCr strain is the sole member of genotype A (8).…”

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An Attenuated Strain of Enterovirus 71 Belonging to Genotype A Showed a Broad Spectrum of Antigenicity with Attenuated Neurovirulence in Cynomolgus Monkeys

Arita¹,

Nagata²,

Iwata³

et al. 2007

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Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and is also sometimes associated with serious neurological disorders. In this study, we characterized the antigenicity and tissue specificity of an attenuated strain of EV71 [EV71(S1-3)], which belongs to genotype A, in a monkey infection model. Three cynomolgus monkeys were inoculated with EV71(S1-3), followed by lethal challenge with the parental virulent strain EV71(BrCr-TR) via an intravenous route on day 45 postinoculation of EV71(S1-3). Monkeys inoculated with EV71(S1-3) showed a mild neurological symptom (tremor) but survived lethal challenge by virulent EV71(BrCr-TR) without exacerbation of the symptom. The immunized monkey sera showed a broad spectrum of neutralizing activity against different genotypes of EV71, including genotypes A, B1, B4, C2, and C4. For the strains examined, the sera showed the highest neutralization activity against the homotype (genotype A) and the lowest neutralization activity against genotype C2. The order of decreasing neutralization activity of sera was as follows: A > B1 > C4 > B4 > C2. To examine the tissue specificity of EV71(S1-3), two monkeys were intravenously inoculated with EV71(S1-3), followed by examination of virus distribution in the central nervous system (CNS) and extraneural tissues. In the CNS, EV71(S1-3) was isolated only from the spinal cord. These results indicate that EV71(S1-3) acts as an effective antigen, although this attenuated strain was still neurotropic when inoculated via the intravenous route.Enterovirus 71 (EV71) is a small nonenveloped virus with a genome of single-strand positive RNA of about 7,500 nucleotides and belongs to the genus Enterovirus of the family Picornaviridae (8, 48). EV71 is classified as Human enterovirus species A along with some coxsackie A (CA) viruses, such as CA10 and CA16 (8, 44). CA10, CA16, and EV71 cause hand, foot, and mouth disease (HFMD) and herpangina. EV71 infection is also sometimes associated with severe neurological diseases, such as brain stem encephalitis and poliomyelitis-like paralysis, mainly in infants and young children (11,34,56). The neuropathogenic features of EV71 were first emphasized during an outbreak in Bulgaria in 1975 in which poliomyelitis-like paralysis was the major symptom (21.1% of patients), with a high fatality rate (29.5%) among the paralytic cases (51). In recent large-scale outbreaks of HFMD in Malaysia (1997) (1, 50) and Taiwan (1998 and2000) (20,28,29,55), several fatal encephalitis cases were reported. In the EV71 outbreak in Taiwan in 1998, out of 129,106 cases of HFMD or herpangina, there were 405 severe cases, including 78 fatal cases (20); thus, the severity rate of this outbreak was Ͻ0.3%. These findings underscore the high neuropathogenicity of EV71 as well as poliovirus (PV), which causes poliomyelitis in 0.1 to 1.0% of infected individuals (reviewed in reference 36).Most of the fatal EV71 cases in Taiwan were in young children (age, Յ5 years) and involved pulmonary edema and/or pulmonary hemorrha...

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“…[5][6][7] Outbreaks of EV71 in the region have been identified in 41% of HFMD cases, 81% of severe cases, and 93% of deaths, resulting in higher rates of complications, neurological disease, and fatalities compared with other causative agents such as CA16. 6,[8][9][10][11][12] It is therefore important to distinguish EV71 from other HFMD strains during the outbreak. 13 In 2011, following the emergence of HFMD outbreaks throughout the Western Pacific Region, the HKSAR Government announced EV71 infection as one of the 47 statutorily notifiable communicable diseases under the Prevention and Control of Disease Ordinance (Central Notification Office).…”

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Best practices to prevent transmission and control outbreaks of hand, foot, and mouth disease in childcare facilities: a systematic review

et al. 2017

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Molecular epidemiology of enterovirus 71 infection in the Western Pacific Region

Cited by 139 publications

References 30 publications

A Strain-Specific Epitope of Enterovirus 71 Identified by Cryo-Electron Microscopy of the Complex with Fab from Neutralizing Antibody

A Strain-Specific Epitope of Enterovirus 71 Identified by Cryo-Electron Microscopy of the Complex with Fab from Neutralizing Antibody

An Attenuated Strain of Enterovirus 71 Belonging to Genotype A Showed a Broad Spectrum of Antigenicity with Attenuated Neurovirulence in Cynomolgus Monkeys

Best practices to prevent transmission and control outbreaks of hand, foot, and mouth disease in childcare facilities: a systematic review

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