Hand, foot, and mouth disease outbreak reported in Singapore

Ahmad, Khabir

doi:10.1016/s0140-6736(05)74253-7

Cited by 61 publications

(48 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The clinical symptoms of HFMD due to EV71 are generally mild and selflimiting; however, EV71 occasionally causes severe neurological diseases, such as brainstem encephalitis and acute flaccid paralysis (9). Recently, epidemic outbreaks of neurovirulent EV71 have been reported mainly in Southeast and East Asia, including Taiwan, Malaysia, Singapore, Japan, and China (10)(11)(12)(13)(14)(15). From 2008 to 2011, the epidemic outbreaks of EV71 in China resulted in approximately 1,900 fatal cases (16).…”

mentioning

confidence: 99%

Functional Comparison of SCARB2 and PSGL1 as Receptors for Enterovirus 71

Yamayoshi

Ohka

Fujii

et al. 2013

J Virol

109

119

View full text Add to dashboard Cite

Human scavenger receptor class B, member 2 (SCARB2), and P-selectin glycoprotein ligand-1 (PSGL1) have been identified to be the cellular receptors for enterovirus 71 (EV71). We compared the EV71 infection efficiencies of mouse L cells that expressed SCARB2 (L-SCARB2) and PSGL1 (L-PSGL1) and the abilities of SCARB2 and PSGL1 to bind to the virus. L-SCARB2 cells bound a reduced amount of EV71 compared to L-PSGL1 cells. However, EV71 could infect L-SCARB2 cells more efficiently than L-PSGL1 cells. The results suggested that the difference in the binding capacities of the two receptors was not the sole determinant of the infection efficiency and that SCARB2 plays an essential role after attaching to virions. Therefore, we examined the viral entry into L-SCARB2 cells and L-PSGL1 cells by immunofluorescence microscopy. In both cells, we detected internalized EV71 virions that colocalized with an early endosome marker. We then performed a sucrose density gradient centrifugation analysis to evaluate viral uncoating. After incubating the EV71 virion with L-SCARB2 cells or soluble SCARB2 under acidic conditions below pH 6.0, we observed that part of the native virion was converted into an empty capsid that lacked both genomic RNA and VP4 capsid proteins. The results suggested that the uncoating of EV71 requires both SCARB2 and an acidic environment and occurs after the internalization of the virus-receptor complex into endosomes. However, the empty capsid formation was not observed after incubation with L-PSGL1 cells or soluble PSGL1 under any of the tested pH conditions. These results indicated that SCARB2 is capable of viral binding, viral internalization, and viral uncoating and that the low infection efficiency of L-PSGL1 cells is due to the inability of PSGL1 to induce viral uncoating. The characterization of SCARB2 as an uncoating receptor greatly contributes to the understanding of the early steps of EV71 infection.

show abstract

mentioning

confidence: 99%

Functional Comparison of SCARB2 and PSGL1 as Receptors for Enterovirus 71

Yamayoshi

Ohka

Fujii

et al. 2013

J Virol

109

119

View full text Add to dashboard Cite

show abstract

“…Although HFMD is generally considered a mildly infectious disease, HFMD caused by EV71, but not by other enteroviruses, is sometimes involved with severe neurological diseases, including brain stem encephalitis and acute flaccid paralysis (23). In recent years, epidemic or sporadic outbreaks of neurovirulent EV71 infections have been reported mainly in Southeast or East Asia, including Taiwan, Malaysia, Singapore, Japan, and China (1,8,11,17,27,38 Human RD cells are highly susceptible to EV71 infection, whereas mouse L929 cells exhibit very low susceptibility. We previously reported the identification of EV71 receptors by genetic complementation of L929 cells with genes transferred from human RD cells (37).…”

mentioning

confidence: 99%

Identification of a Human SCARB2 Region That Is Important for Enterovirus 71 Binding and Infection

Yamayoshi

Koike

2011

J Virol

View full text Add to dashboard Cite

We previously identified human scavenger receptor class B, member 2 (SCARB2), as a cellular receptor for enterovirus 71 (EV71). Expression of human SCARB2 (hSCARB2) permitted mouse L929 cells to efficiently bind to virions and to produce both viral proteins and progeny viruses upon EV71 infection. Mouse Scarb2 (mScarb2) exhibited 85.8% amino acid identity and 99.9% similarity to hSCARB2. The expression of mScarb2 in L929 cells conferred partial susceptibility. Very few virions bound to mScarb2-expressing cells. The viral titer in L929 cells expressing mScarb2 was approximately 40-to 100-fold lower than that in L929 cells expressing hSCARB2. Using hSCARB2-mScarb2 chimeric mutants, we attempted to map the region that was important for efficient EV71 infection. L929 cells expressing chimeras that carried amino acids 142 to 204 from the human sequence were susceptible to EV71, while chimeras that carried the mouse sequence in this region were not. Moreover, this region was also critical for binding to virions. The determination of this region in hSCARB2 that is important for EV71 binding and infection greatly contributes to the understanding of virus-receptor interactions. Further studies will clarify the early steps of EV71 infection.Enterovirus 71 (EV71), together with coxsackievirus A16 (CVA16), belongs to human enterovirus species A of the genus Enterovirus within the family Picornaviridae (28). The virus contains a single-stranded, positive-sense RNA surrounded by an icosahedral capsid assembled from 60 copies of each of the four structural proteins: VP1, VP2, VP3, and VP4 (32). EV71 was first isolated from patients with neurological diseases, including fatal encephalitis and aseptic meningitis, in California from 1969 to 1972 (33). Later studies revealed that EV71 is associated with hand-foot-and-mouth disease (HFMD) in young children and infants (6, 13). Although HFMD is generally considered a mildly infectious disease, HFMD caused by EV71, but not by other enteroviruses, is sometimes involved with severe neurological diseases, including brain stem encephalitis and acute flaccid paralysis (23). In recent years, epidemic or sporadic outbreaks of neurovirulent EV71 infections have been reported mainly in Southeast or East Asia, including Taiwan, Malaysia, Singapore, Japan, and China (1,8,11,17,27,38 Human RD cells are highly susceptible to EV71 infection, whereas mouse L929 cells exhibit very low susceptibility. We previously reported the identification of EV71 receptors by genetic complementation of L929 cells with genes transferred from human RD cells (37). Briefly, we established two EV71-susceptible cell lines that carried a portion of human genomic DNA. By identifying the integrated human DNA in one of the transformants, Ltr051 cells, we have shown that scavenger receptor class B, member 2 (SCARB2), is a cellular receptor for EV71. SCARB2 serves as a receptor for all EV71 isolates tested. EV71 infection in the SCARB2-expressing L929 cell line is as efficient as that in the RD cell line (37). We have also f...

show abstract

“…The recent HFMD outbreak in Singapore in October 2000 affected several thousand children and resulted in four deaths (1). In Singapore, HFMD is endemic and the disease manifests mainly as febrile upper respiratory illness and herpangina.…”

mentioning

confidence: 99%

Direct Detection of Enterovirus 71 (EV71) in Clinical Specimens from a Hand, Foot, and Mouth Disease Outbreak in Singapore by Reverse Transcription-PCR with Universal Enterovirus and EV71-Specific Primers

et al. 2002

View full text Add to dashboard Cite

A recent outbreak of hand, foot, and mouth disease in Singapore in 2000 affected several thousand children and resulted in four deaths. The aim of this study was to determine the applicability of reverse transcription-PCR (RT-PCR) with universal pan-enterovirus primers and enterovirus 71 (EV71) type-specific primers for the direct detection of enteroviruses in clinical specimens derived from this outbreak. With the universal primers, EV71 RNA sequences were successfully detected by RT-PCR and direct sequencing in 71% of positive specimens. Three pairs of EV71 type-specific primers were evaluated for rapid detection of EV71 directly from clinical specimens and cell culture isolates. By using a seminested RT-PCR strategy, specific identification of EV71 sequences directly in clinical specimens was achieved, with a detection rate of 53%. In contrast, cell culture could isolate EV71 in only 20% of positive specimens. EV71 was detected directly from brain, heart, and lung specimens of two deceased siblings. Although more than one type of enterovirus was identified in clinical specimens from this outbreak, 90% of the enteroviruses were confirmed as EV71. The data demonstrate the clinical applicability of pan-enterovirus and seminested RT-PCR for the detection of EV71 RNA directly from clinical specimens in an outbreak situation.Hand, foot, and mouth disease (HFMD) is of serious concern in the Asia-Pacific region as a result of two major epidemics with high fatalities in Malaysia and Taiwan in recent years (6,7,11). The recent HFMD outbreak in Singapore in October 2000 affected several thousand children and resulted in four deaths (1). In Singapore, HFMD is endemic and the disease manifests mainly as febrile upper respiratory illness and herpangina. There have been reports of some children with acute flaccid paralysis who fully recovered (12). The classical diagnostic method for enteroviruses is propagation by cell culture followed by neutralization with specific antisera to confirm the serotype. Cell culture from clinical specimens is considered the "gold standard," but the procedure is time-consuming and may take a few weeks. Furthermore, some enteroviruses replicate poorly in cell cultures, require several passages, or may be untypeable (9).In view of its high sensitivity and specificity, reverse transcription-PCR (RT-PCR) is beneficial for the rapid detection of enterovirus 71 (EV71) in outbreak situations. The rapid establishment of enteroviral etiology would eliminate the unnecessary use of antibiotics and lead to better patient management. Early diagnosis can help to limit the spread of the disease in the community during an outbreak. The aim of this study was to identify the etiological agents involved in the HFMD outbreak. We investigated the applicability of RT-PCR by using universal pan-enterovirus and type-specific primers for the direct detection of EV71 in clinical specimens. Direct sequencing of RT-PCR products amplified from the 5Ј untranslated region (5Ј UTR) by using universal primers (10, 16) was com...

show abstract

Hand, foot, and mouth disease outbreak reported in Singapore

Cited by 61 publications

References 0 publications

Functional Comparison of SCARB2 and PSGL1 as Receptors for Enterovirus 71

Functional Comparison of SCARB2 and PSGL1 as Receptors for Enterovirus 71

Identification of a Human SCARB2 Region That Is Important for Enterovirus 71 Binding and Infection

Direct Detection of Enterovirus 71 (EV71) in Clinical Specimens from a Hand, Foot, and Mouth Disease Outbreak in Singapore by Reverse Transcription-PCR with Universal Enterovirus and EV71-Specific Primers

Contact Info

Product

Resources

About