Change of Major Genotype of Enterovirus 71 in Outbreaks of Hand-Foot-and-Mouth Disease in Taiwan between 1998 and 2000

Wang, Jen Ren; Tuan, Yen-Chang; Tsai, Huey‐Pin; Yan, Jing-Jou; Liu, Ching-Chuan; Su, Ih‐Jen

doi:10.1128/jcm.40.1.10-15.2002

Cited by 164 publications

(151 citation statements)

References 13 publications

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“…There have also been reports of antigenic heterogeneity among EV71 isolates, including a maximum difference in neutralization titers of 32-fold between different rabbit sera after EV71 inoculation (19). Frequent changes in the genotype of circulating EV71 may in part reflect antigenic variation in cross-neutralization between genotypes that may be critical for the perpetuation of EV71 (27,37,41,55).…”

Section: Discussionmentioning

confidence: 99%

“…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%.…”

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confidence: 99%

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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

J Virol

125

100

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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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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

J Virol

125

100

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“…It is mainly caused by Coxsackie virus (A16), human enterovirus (EV71) or other enteroviruses including Coxsackie viruses A4, 5, 9, 10, B2 and 5 (McMinn et al, 2001). Recent outbreaks of HFMD in many areas such as Taiwan (Wang et al, 2002), Japan (Fujimoto et al, 2002), Malaysia (Chua et al, 2011) and China (Zhang et al, 2009) were caused by Enterovirus 71 (EV71) which includes a variety of neurological diseases, including aseptic meningitis, encephalitis, and poliomyelitis-like paralysis (Knipe et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Modelling the effects of contaminated environments on HFMD infections in mainland China

2016

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“…Several receptors or attachment molecules for EV71 have been identified, including scavenger receptor B2 (SCARB2), P-selectin glycoprotein ligand-1 (PSGL-1), sialylated glycoprotein, dendritic cell-specific ICAM 3-grabbing nonintegrin, annexin II, vimentin, and polysaccharide (heparin sulfate) (7)(8)(9)(10)(11)(12)(13). EV71 strains can be divided into different subgenotypes based on sequence homology (14). Human SCARB2 (hSCARB2) mediates the entry of EV71 strains or genotypes tested (15).…”

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confidence: 99%

Cell Surface Nucleolin Facilitates Enterovirus 71 Binding and Infection

Wang

Huang

et al. 2015

J Virol

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Because the pathogenesis of enterovirus 71 (EV71) remains mostly ambiguous, identifying the factors that mediate viral binding and entry to host cells is indispensable to ultimately uncover the mechanisms that underlie virus infection and pathogenesis. Despite the identification of several receptors/attachment molecules for EV71, the binding, entry, and infection mechanisms of EV71 remain unclear. Herein, we employed glycoproteomic approaches to identify human nucleolin as a novel binding receptor for EV71. Glycoproteins purified by lectin chromatography from the membrane extraction of human cells were treated with sialidase, followed by immunoprecipitation with EV71 particles. Among the 16 proteins identified by tandem mass spectrometry analysis, cell surface nucleolin attracted our attention. We found that EV71 interacted directly with nucleolin via the VP1 capsid protein and that an antinucleolin antibody reduced the binding of EV71 to human cells. In addition, the knockdown of cell surface nucleolin decreased EV71 binding, infection, and production in human cells. Furthermore, the expression of human nucleolin on the cell surface of a mouse cell line increased EV71 binding and conferred EV71 infection and production in the cells. These results strongly indicate that human nucleolin can mediate EV71 binding to and infection of cells. Our findings also demonstrate that the use of glycoproteomic approaches is a reliable methodology to discover novel receptors for pathogens. IMPORTANCEOutbreaks of EV71 have been reported in Asia-Pacific countries and have caused thousands of deaths in young children during the last 2 decades. The discovery of new EV71-interacting molecules to understand the infection mechanism has become an emergent issue. Hence, this study uses glycoproteomic approaches to comprehensively investigate the EV71-interacting glycoproteins. Several EV71-interacting glycoproteins are identified, and the role of cell surface nucleolin in mediating the attachment and entry of EV71 is characterized and validated. Our findings not only indicate a novel target for uncovering the EV71 infection mechanism and anti-EV71 drug discovery but also provide a new strategy for virus receptor identification.

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Change of Major Genotype of Enterovirus 71 in Outbreaks of Hand-Foot-and-Mouth Disease in Taiwan between 1998 and 2000

Abstract: Two outbreaks of hand-foot-and-mouth disease (HFMD) occurred in Taiwan

Cited by 164 publications

References 13 publications

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

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

Modelling the effects of contaminated environments on HFMD infections in mainland China

Cell Surface Nucleolin Facilitates Enterovirus 71 Binding and Infection

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