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Fulltext Comparative genetic analysis of VP4, VP1 and 3D gene regions of enterovirus 71 and coxsackievirus A16 circulating in Malaysia between 1997-2008

Chan YF, Wee KL, Chiam CW, Khor CS, Chan SY, Amalina W MZ, et al.

Trop Biomed, 2012 Sep;29(3):451-66.
PMID: 23018509 MyJurnal

Three genomic regions, VP4 capsid, VP1 capsid and 3D RNA polymerase of human enterovirus 71 (EV-71) and coxsackievirus A16 (CV-A16) were sequenced to understand the evolution of these viruses in Malaysia. A total of 42 EV-71 and 36 CV-A16 isolates from 1997- 2008 were sequenced. Despite the presence of many EV-71 subgenotypes worldwide, only subgenotypes B3, B4, B5, C1 and C2 were present in Malaysia. Importation of other subgenotypes such as C3, C4/D and C5 from other countries was infrequent. For CV-A16, the earlier subgenotype B1 was replaced by subgenotypes B2a and the recent B2c. Subgenotype B2a was present throughout the study while B2c only emerged in 2005. No genetic signatures could be attributed to viral virulence suggesting that host factors have a major role in determining the outcome of infection. Only three EV-71 B3 isolates showed non-consistent phylogeny in the 3D RNA polymerase region which indicated occurrence of recombination in EV-71. High genetic diversity was observed in the Malaysian EV-71 but Malaysian CV-A16 showed low genetic diversity in the three genomic regions sequenced. EV-71 showed strong purifying selection, but that occurred to a lesser extent in CV-A16.

Matched MeSH terms: Hand, Foot and Mouth Disease/epidemiology; Hand, Foot and Mouth Disease/virology*
Fulltext Pharmacological perturbation of CXCL1 signaling alleviates neuropathogenesis in a model of HEVA71 infection

Gunaseelan S, Ariffin MZ, Khanna S, Ooi MH, Perera D, Chu JJH, et al.

Nat Commun, 2022 Feb 16;13(1):890.
PMID: 35173169 DOI: 10.1038/s41467-022-28533-z

Hand, foot and mouth disease (HFMD) caused by Human Enterovirus A71 (HEVA71) infection is typically a benign infection. However, in minority of cases, children can develop severe neuropathology that culminate in fatality. Approximately 36.9% of HEVA71-related hospitalizations develop neurological complications, of which 10.5% are fatal. Yet, the mechanism by which HEVA71 induces these neurological deficits remain unclear. Here, we show that HEVA71-infected astrocytes release CXCL1 which supports viral replication in neurons by activating the CXCR2 receptor-associated ERK1/2 signaling pathway. Elevated CXCL1 levels correlates with disease severity in a HEVA71-infected mice model. In humans infected with HEVA71, high CXCL1 levels are only present in patients presenting neurological complications. CXCL1 release is specifically triggered by VP4 synthesis in HEVA71-infected astrocytes, which then acts via its receptor CXCR2 to enhance viral replication in neurons. Perturbing CXCL1 signaling or VP4 myristylation strongly attenuates viral replication. Treatment with AZD5069, a CXCL1-specific competitor, improves survival and lessens disease severity in infected animals. Collectively, these results highlight the CXCL1-CXCR2 signaling pathway as a potential target against HFMD neuropathogenesis.

Matched MeSH terms: Hand, Foot and Mouth Disease/pathology*; Hand, Foot and Mouth Disease/virology
RT-PCR, nucleotide, amino acid and phylogenetic analyses of enterovirus type 71 strains from Asia

Singh S, Chow VT, Chan KP, Ling AE, Poh CL

J Virol Methods, 2000 Aug;88(2):193-204.
PMID: 10960707

A specific and sensitive method based on RT-PCR was developed to detect enterovirus 71 (EV71) from patients with hand, foot and mouth disease, myocarditis, aseptic meningitis and acute flaccid paralysis. RT-PCR primers from conserved parts of the VP1 capsid gene were designed on the basis of good correlation with sequences of EV71 strains. These primers successfully amplified 44 strains of EV71 including 34 strains isolated from Singapore in 1997 and 1998, eight strains from Malaysia isolated in 1997 and 1998, one Japanese strain and the neurovirulent strain EV71/7423/MS/87. RT-PCR of 30 strains of other enteroviruses including coxsackievirus A and B, and echoviruses failed to give any positive amplicons. Hence, RT-PCR with these primers showed 100% correlation with serotyping. Direct sequencing of the RT-PCR products of 20 EV71 strains revealed a distinct cluster with two major subgroups, thus enabling genetic typing of the viruses. The genetic heterogeneity of these strains culminated in amino acid substitutions within the VP1, VP2 and VP3 regions. The sequencing of a 2.9 kb fragment comprising the capsid region and the major part of 5' UTR of two Singapore strains revealed that they belonged to a group distinct from the prototype EV71/BrCr strain and the EV71/7423/MS/87 strain. The dendrogram generated from 341 bp fragments within the VP1 region revealed that the strains of Singapore, Malaysia and Taiwan belong to two entirely different EV71 genogroups, distinct from the three genogroups identified in another recent study.

Matched MeSH terms: Hand, Foot and Mouth Disease/virology*
Enterovirus-Specific Anti-peptide Antibodies

Poh CL, Kirk K, Chua HN, Grollo L

Methods Mol Biol, 2015;1348:341-50.
PMID: 26424285 DOI: 10.1007/978-1-4939-2999-3_29

Enterovirus 71 (EV-71) is the main causative agent of hand, foot, and mouth disease (HFMD) which is generally regarded as a mild childhood disease. In recent years, EV71 has emerged as a significant pathogen capable of causing high mortalities and severe neurological complications in large outbreaks in Asia. A formalin-inactivated EV71 whole virus vaccine has completed phase III trial in China but is currently unavailable clinically. The high cost of manufacturing and supply problems may limit practical implementations in developing countries. Synthetic peptides representing the native primary structure of the viral immunogen which is able to elicit neutralizing antibodies can be made readily and is cost effective. However, it is necessary to conjugate short synthetic peptides to carrier proteins to enhance their immunogenicity. This review describes the production of cross-neutralizing anti-peptide antibodies in response to immunization with synthetic peptides selected from in silico analysis, generation of B-cell epitopes of EV71 conjugated to a promiscuous T-cell epitope from Poliovirus, and evaluation of the neutralizing activities of the anti-peptide antibodies. Besides neutralizing EV71 in vitro, the neutralizing antibodies were cross-reactive against several Enteroviruses including CVA16, CVB4, CVB6, and ECHO13.

Matched MeSH terms: Hand, Foot and Mouth Disease
Fulltext Risk Factors for Enterovirus A71 Seropositivity in Rural Indigenous Populations in West Malaysia

NikNadia N, Sam IC, Khaidir N, Ngui R, Lim YA, Goh XT, et al.

PLoS One, 2016;11(2):e0148767.
PMID: 26866912 DOI: 10.1371/journal.pone.0148767

Enterovirus A71 (EV-A71), which is transmitted by the fecal-oral route, causes hand, foot and mouth disease and, rarely, severe neurological complications. In Malaysia, the indigenous rural community (Orang Asli) has a high prevalence of parasitic diseases due to poor sanitation, water supply and hygiene practices. This cross-sectional study compared the seroepidemiology of EV-A71 among rural Orang Asli and urban Kuala Lumpur populations in West Malaysia, and determined the risk factors associated with EV-A71 seropositivity in rural Orang Asli. Seropositive rates were determined by neutralization assay. EV-A71 seropositivity was strongly associated with increasing age in both populations. Rural Orang Asli children ≤12 years had significantly higher EV-A71 seropositivity rates than urban Kuala Lumpur children (95.5% vs 57.6%, P < 0.001), and also higher rates in the age groups of 1-3, 4-6 and 7-12 years. Multivariate analysis confirmed that age ≤12 years (adjusted OR 8.1, 95% CI 3.2-20.7, P < 0.001) and using untreated water (adjusted OR 6.2, 95% CI 2.3-16.6, P < 0.001) were independently associated with EV-A71 seropositivity in the Orang Asli population. Supply of clean drinking water may reduce the risk of EV-A71 infection. With significantly higher EV-A71 seropositive rates, younger rural children should be a priority target for future vaccination programs in Malaysia.

Matched MeSH terms: Hand, Foot and Mouth Disease
Fulltext Echovirus serotypes circulating in Malaysia from 2014 to 2019

Manisya Zauri Abdul Wahid, Tengku Rogayah T. Abd. Rashid, Hariyati Md. Ali, Hamadah Mohd Shafiff, Mohd. Shamsul Samsuddin, Syarifah Nur Aisyatun Syed Mohd Salleh, et al.

Malaysian Journal of Medicine and Health Sciences, 2019;15(106):91-91.
MyJurnal

Introduction:Echoviruses are Enteroviruses (HEVs) that infect millions of people annually worldwide, primarily paediatrics. These viruses are frequently associated with outbreaks and sporadic cases of viral meningitis, enceph-alitis, paralysis, myocarditis, severe systemic infections; and hand-foot-mouth disease. This study is a retrospective study to identify Echovirus serotypes circulating in Malaysia from January 2014 to June 2019, and their roles in outbreak prediction. This study investigated the Echovirus serotypes circulating in Malaysia from January 2014 to June 2019. Methods: A total of 13,855 inpatient samples consisting respiratory secretion, stool, tissue and body fluid from around the country were received by the Virology Unit, Institute for Medical Research between January 2014 and June 2019. The presence of HEV’s RNA was detected by qPCR. The identified positive sample was further isolated by cell culture and identified by Immunofluorescence Assay (IFA). The IFA positive samples were subjected to amplification of partial VP4 gene by RT-PCR, and proceeded to Sanger sequencing for phylogenetic analysis by using ChromasPro and MEGA Software. The sequence generated were analysed by BLAST to confirm the sequence serotypes generated. Results: Echovirus genome was detected in 0.35% (37/10,681) of the patients. The circulating Echovirus subtypes in Malaysia between January 2014 and June 2019 were Echo-11 (43.2%; 16/37), followed by Echo-6 (16.2%; 6/37); 8.1% (3/37) of Echo-7 and Echo-13, respectively. Meanwhile, other types of Echoviruses (24.3%; 9/37) such as Echo 3-5, Echo-14, Echo-16, Echo-18, Echo-25 and Echo-30 were also detected in this study. Conclusion: In this study, it has been found that Echovirus 11 serotype is the most predominant Echovirus serotype circulating in Malaysia between January 2014 and June 2019. It has been reported to cause severe diseases, such as aseptic meningitis. Therefore, the identification of circulating serotypes of Echovirus is critical to predict the Echovi-rus outbreak and to reduce the risk of developing severe disease in Malaysia.

Matched MeSH terms: Hand, Foot and Mouth Disease
Immune responses against enterovirus A71 infection: Implications for vaccine success

Aw-Yong KL, NikNadia NMN, Tan CW, Sam IC, Chan YF

Rev Med Virol, 2019 09;29(5):e2073.
PMID: 31369184 DOI: 10.1002/rmv.2073

Enterovirus A71 (EV-A71) from the Picornaviridae family is an important emerging pathogen causing hand, foot, and mouth disease (HFMD) outbreaks worldwide. EV-A71 also caused fatal neurological complications in young children especially in Asia. On the basis of seroepidemiological studies from many Asian countries, EV-A71 infection is very common. Children of very young age are particularly vulnerable. Large-scale epidemics that occur every 3 to 4 years are associated with accumulation of an immunologically naive younger population. Capsid proteins especially VP1 with the presence of major B- and T-cell epitopes are the most antigenic proteins. The nonstructural proteins mainly contribute to T-cell epitopes that induce cross-reactive immune responses against other enteroviruses. Dominant epitopes and their neutralization magnitudes differ in mice, rabbits, and humans. Neutralizing antibody is sufficient for immune protection, but poorer cellular immunity may lead to severe neurological complications and deaths. Some chemokines/cytokines are consistently found in severely ill patients, for example, IL-6, IL-10, IL-17A, MCP-1, IL-8, MIG, IP-10, IFN-γ, and G-CSF. An increase in white cell counts is a risk factor for severe HFMD. Recent clinical trials on EV-A71 inactivated vaccine showed >90% efficacy and a robust neutralization response that was protective, indicating neutralizing antibody correlates for protection. No protection against other enteroviruses was observed. A comprehensive understanding of the immune responses to EV-A71 infection will benefit the development of diagnostic tools, potential therapeutics, and subunit vaccine candidates. Future development of a multivalent enterovirus vaccine will require knowledge of correlates of protection, understanding of cross-protection and memory T-cell responses among enteroviruses.

Matched MeSH terms: Hand, Foot and Mouth Disease
Fulltext Isolation and molecular characterization of coxsackievirus A6 and coxsackievirus A16 from a case of recurrent Hand, Foot and Mouth Disease in Mumbai, Maharashtra, India, 2018

Saxena VK, Pawar SD, Qureshi THIH, Surve P, Yadav P, Nabi F, et al.

Virusdisease, 2020 Mar;31(1):56-60.
PMID: 32206699 DOI: 10.1007/s13337-020-00567-1

Hand, Foot and Mouth Disease (HFMD) is caused by multiple Enterovirus (EV) serotypes mainly coxsackievirus A6 (CV-A6), coxsackievirus A16 (CV-A16) and Enterovirus 71 (EV-A71). Recurrent HFMD infections are rarely reported. An unusual rise in HFMD cases was reported in Mumbai during May-June 2018. Stool and throat swab specimens were referred from seven children from two hospitals for laboratory diagnosis. The age group of cases ranged from 9 months to 5 years with median age 13 months. Out of seven cases, three were males and four females. One 13-month-old female case was reported twice within 21 days. Stool, throat swab specimens were tested by pan enterovirus RT-PCR and also by virus isolation using human rhabdomyosarcoma cell line for detection of Enteroviruses. Out of seven HFMD cases, CV-A6 and CV-A16 viruses were isolated from five and two cases respectively. The phylogenetic analysis of CV-A6 viruses showed their similarity with CV-A6 viruses from Finland and China, whereas the two CV-A16 isolates showed similarity with those from Japan, France, China, Sarawak and Thailand. For the recurrent HFMD case, CV-A6 and CV-A16 were isolated from the stool specimens collected during the first and second episodes, respectively. There are no reports of isolation and molecular characterization of CV-A6 and CV-A16 viruses from recurrent HFMD cases. The present study reports molecular characterization of two Enterovirus serotypes CV-A6 and CV-A16 from a recurrent HFMD case, highlighting need of virological and molecular surveillance of HFMD.

Matched MeSH terms: Hand, Foot and Mouth Disease
Recombinant Enterovirus 71 Viral Protein 1 Fused to a Truncated Newcastle Disease Virus NP (NPt) Carrier Protein

Mustafa S, Abd-Aziz N, Saw WT, Liew SY, Yusoff K, Shafee N

Vaccines (Basel), 2020 Dec 07;8(4).
PMID: 33297428 DOI: 10.3390/vaccines8040742

Enterovirus 71 (EV71) is the major causative agent in hand, foot, and mouth disease (HFMD), and it mainly infects children worldwide. Despite the risk, there is no effective vaccine available for this disease. Hence, a recombinant protein construct of truncated nucleocapsid protein viral protein 1 (NPt-VP1198-297), which is capable of inducing neutralizing antibody against EV71, was evaluated in a mouse model. Truncated nucleocapsid protein Newcastle disease virus that was used as immunological carrier fused to VP1 of EV71 as antigen. The recombinant plasmid carrying corresponding genes was constructed by recombinant DNA technology and the corresponding protein was produced in Escherichia coli expression system. The recombinant NPt-VP1198-297 protein had elicited neutralizing antibodies against EV71 with the titer of 1:16, and this result is higher than the titer that is elicited by VP1 protein alone (1:8). It was shown that NPt containing immunogenic epitope(s) of VP1 was capable of inducing a greater functional immune response when compared to full-length VP1 protein alone. It was capable to carry larger polypeptide compared to full-length NP protein. The current study also proved that NPt-VP1198-297 protein can be abundantly produced in recombinant protein form by E. coli expression system. The findings from this study support the importance of neutralizing antibodies in EV71 infection and highlight the potential of the recombinant NPt-VP1198-297 protein as EV71 vaccine.

Matched MeSH terms: Hand, Foot and Mouth Disease
Assessment on Hand Hygiene Knowledge and Practices Among Pre-school Children in Klang Valley

Tengku Jamaluddin TZM, Mohamed NA, Mohd Rani MD, Ismail Z, Ramli S, Faroque H, et al.

Glob Pediatr Health, 2020;7:2333794X20976369.
PMID: 33335950 DOI: 10.1177/2333794X20976369

Background. Pre-school children are at a higher risk to acquire infectious diseases such as hand, foot and mouth disease due to their immature immune system. Good hand hygiene prevents transmission of infectious diseases. This study aimed to determine the knowledge and practices of hand hygiene among pre-schoolers. Methods. In this prospective, multi-center study, the pre-schools were selected according to the selection criteria. A questionnaire consisting of socio-demographics, knowledge and practices of hand hygiene were administered via face-to-face interview during the pre- and post-intervention period. A total of 435 pre-schoolers aged 5 and 6 years old from 2 pre-schools within Klang Valley, School P (test group) and School C (control group) were involved in this study. The test group was provided with comprehensive hand hygiene education including video on proper handwashing technique during the 2 months intervention period, whereas the control group did not receive any form of intervention. The data were statistically analyzed using descriptive analysis and independent t-test. Results. Majority of pre-schoolers gained knowledge of handwashing from their parents. However, only 63% demonstrated good handwashing technique. Test group were significantly better (P hand hygiene routine score. Conclusion. A comprehensive hand hygiene education program should include proper handwashing facilities, resources, and awareness of the care-givers in instilling and sustaining good hand hygiene behavior.

Matched MeSH terms: Hand, Foot and Mouth Disease
Fulltext Pathological findings in a mouse model for Coxsackievirus A16 infection

Hooi, Yuan Teng, Ong, Kien Chai, Perera, David, Wong, Kum Thong

Neurology Asia, 2015;20(4):343-347.
MyJurnal

Coxsackievirus A16 (CV-A16) is the leading cause of hand-foot-mouth disease (HFMD), which usually
presents as mild and self-limiting symptoms in young children. Rarely, CV-A16 has been reported
to cause severe and fatal neurological complications but little is known about these complications.
In the present study, 1-day and 7-day old mouse models of CV-A16 were developed using a clinical
strain via subcutaneous inoculation. All infected mice exhibited clinical signs of infection, including
reduced mobility, limb weakness and paralysis between 3 to 6 days post-infection. Pathologically,
the main organs involved were the central nervous system (CNS), skeletal muscles and brown fat. In
the CNS, viral antigens as demonstrated by immunohistochemistry, were localized mainly to neurons
in the brain stem and spinal cord, suggesting that CV-A16 is neurotropic although inflammation is
very mild. The skeletal muscles showed necrosis and myositis due to viral infection as evidenced by
the dense viral antigens. Focal viral antigens were also detected in the brown fat. These preliminary
pathological findings indicate that our mouse models can be further developed to be useful models
for pathogenesis studies, and vaccine and anti-viral drug evaluation.

Matched MeSH terms: Hand, Foot and Mouth Disease
Fulltext The hand, foot and mouth disease (HFMD) outbreak in the state of Johor, Malaysia in the year 2000

Badrul Hisham Abd Samad, Nooraini Baba, Mohd.Raili Suhaili, Prathapa Senan, C., Daud Abd.Rahim

Malaysian Journal of Public Health Medicine, 2003;3(1):68-72.
MyJurnal

The hand, foot, and mouth disease (HFMD) outbreak occurred in the state of Johor, Malaysia in the months 0f October and November 2000 aber the HFMD outbreak started in Singapore in September 2000. The HFMD notification and investigation forms sent to the Epidemiology Unit of the Johor Health Department from district health offices and hospitals during the outbreak were analysed. Patients’ specimens were sent to the Institute for Medical Research, Kuala Lumpur and the Universiti Malaya Medical Centre, Kuala Lumpur for viral isolation. A total of 1,122 HFMD cases were notified during the outbreak period with 2 deaths giving 0.2% casefatality rate. From all the cases, 544 (48.5%) patients were admitted to the hospital while the rest were treated as outpatients. Majority (81.7%) of children with HFMD were aged below 5 years old with the commonest age group (46.9%) being between 1 to 2 years old. Sixty-eight patients had positive specimens for viral isolation belonging to enteroviruses namely Enterovirus 71 (43 cases), Coxsackievirus Type A16 (11), Echovirus 7 (3), and Coxsackievirus Type B (2); and non-enteroviruses namely Herpes Simplex Virus Type 1
(5), and Adenovirus (4). Fever and mouth ulcer were the two most common symptoms among HFMD children but vesicles on palms and soles were more common than rashes in children with positive enteroviral isolation.

Study site: University Malaya Medical Centre (UMMC)

Matched MeSH terms: Hand, Foot and Mouth Disease
Molecular surveillance of coxsackievirus A16 reveals the emergence of a new clade in mainland China

Chen L, Yao XJ, Xu SJ, Yang H, Wu CL, Lu J, et al.

Arch Virol, 2018 Nov 29.
PMID: 30498962 DOI: 10.1007/s00705-018-4112-3

Coxsackievirus A16 (CV-A16) of the genotypes B1a and B1b have co-circulated in mainland China in the past decades. From 2013 to 2017, a total of 3,008 specimens from 3,008 patients with mild hand, foot, and mouth disease were collected in the present study. Viral RNA was tested for CV-A16 by a real-time RT-PCR method, and complete VP1 sequences and full-length genome sequences of CV-A16 strains from this study were determined by RT-PCR and sequencing. Sequences were analyzed using a series of bioinformatics programs. The detection rate for CV-A16 was 4.1%, 25.9%, 10.6%, 28.1% and 12.9% in 2013, 2014, 2015, 2016 and 2017, respectively. Overall, the detection rate for CV-A16 was 16.5% (497/3008) in this 5-year period in Shenzhen, China. One hundred forty-two (142/155, 91.6%) of the 155 genotype B1 strains in the study belonged to subgenotype B1b, and 13 (13/155, 8.4%) strains belonged to subgenotype B1a. Two strains (CVA16/Shenzhen174/CHN/2017 and CVA16/Shenzhen189/CHN/2017) could not be assigned to a known genotype. Phylogenetic analysis of these two strains and other Chinese CV-A16 strains indicated that these two CV-A16 strains clustered independently in a novel clade whose members differed by 8.4%-11.8%, 8.4%-12.1%, and 14.6%-14.8% in their nucleotide sequences from those of Chinese B1a, B1b, and genotype D strains, respectively. Phylogenetic analysis of global CV-A16 strains further indicated that the two novel CV-A16 strains from this study grouped in a previously uncharacterized clade, which was designated as the subgenogroup B3 in present study. Meanwhile, phylogenetic reconstruction revealed two other new genotypes, B1d and B4, which included a Malaysian strain and two American strains, respectively. The complete genome sequences of the two novel CV-A16 strains showed the highest nucleotide sequence identity of 92.3% to the Malaysian strain PM-15765-00 from 2000. Comparative analysis of amino acid sequences of the two novel CV-A16 strains and their relatives suggested that variations in the nonstructural proteins may play an important role in the evolution of modern CV-A16.

Matched MeSH terms: Hand, Foot and Mouth Disease
Fulltext Hypoxia and therapeutic treatment of EV-A71 with an immune modulator TLR7 agonist in a new immunocompetent mouse model

Liou AT, Liao CC, Chou SF, Chang YS, Chang CS, Shih C

J Biomed Sci, 2019 Nov 11;26(1):93.
PMID: 31711481 DOI: 10.1186/s12929-019-0585-y

BACKGROUND: Enterovirus 71 (EV71 or EV-A71) was first identified in California about half a century ago. In recent years, outbreaks of EV-A71 were prevalent worldwide, including Taiwan, Malaysia, Singapore, Japan, and China. Between 2008 and 2011, China alone reported 1894 deaths associated with EV-A71 infection. In mild cases, EV-A71 can cause herpangina and hand-foot-and-mouth disease (HFMD). However, in severe cases, it could cause neurological disorders, including meningitis and encephalitis. Cardiopulmonary failure is common among hospitalized children with EV-A71 infection. No effective FDA-approved therapeutics against EV-A71 are clinically available.
METHODS: We report the establishment of an immunocompetent wild type strain 129 (wt-129) mouse model, which can be cross-species infected with human EV-A71 clinical isolates via an intraperitoneal route.
RESULTS: One intriguing disease phenotype of this new model is the development of characteristic "White-Jade" patches in the muscle, which lost sporadically the normal pink color of uninfected muscle. Viral VP1 protein and massive leukocyte infiltration were detected in muscles with or without white-jades. We demonstrated further that hypoxia is a general phenomenon associated with white-jades in both immunocompetent and immunodeficient mouse models. Therefore, hypoxia appears to be a feature intrinsic to EV-A71 infection, irrespective of its host's immunogenetic background. To date, no effective treatment for EV-A71 is available. Here, using this new wt-129 mouse model, we showed that timely treatment with compound R837 (a TLR7 immune modulator) via oral or intraperitoneal routes, rescued the hypoxia, limb paralysis, and death at a high therapeutic efficacy.
CONCLUSIONS: In this new immunocompetent mouse 129 model, we observed an unexpected white-jade phenotype and its associated hypoxia. The successful treatment with TLR7 immune modulators via an oral route, provide us a new research direction for EV-A71 basic science and translational research. It remains an open issue whether R837 or its related compounds, will be a promising drug candidate in clinical trials in EV-A71 endemic or epidemic areas in the future.

Matched MeSH terms: Hand, Foot and Mouth Disease
Fulltext Virological investigation of genetic variation of enterovirus type 71 in hand, foot and mouth disease

Wang Y, Li Y, Yang Y, Peng C, Fu X, Gu X, et al.

Exp Ther Med, 2020 Jul;20(1):543-549.
PMID: 32537012 DOI: 10.3892/etm.2020.8728

The aim of the present study was to analyze the sequence of the VP1 gene in enterovirus 71 (EV71) isolates and to explore their genetic evolution, so as to provide a scientific basis for the clinical prevention and treatment of hand, foot and mouth disease. The fecal samples of 590 patients with suspected hand, foot and mouth disease treated at Yan'an Hospital (Kunming, China) between January 2015 and December 2016 were collected and EV71 nucleic acid was detected by fluorescence PCR. The viral RNA of EV71-positive samples was extracted, the VP1 gene was amplified by PCR and the products were sequenced. The VP1 gene sequence was analyzed using DNAMAN and MEGA (version 4.0) software and homologous modeling was performed using Pymol software. A total of 50 EV71-positive samples were identified and the detection rate was 8.47% (50/590 cases). All of the 50 EV71 strains were of the C4 subtype. The genetic distance between the strains detected in the present study and EV71 strains detected in Beijing, Anhui and Malaysia was 0.01-0.03, while that between the strains detected in the present study and Australian strains was 2.11. Homologous modeling indicated that the amino acid sequence of the VP1 gene of the detected strains had a H144Y mutation. There was no significant genetic variation in the EV71 strain within the 2-year period. In conclusion, the EV71 strains detected in the present study was similar to that detected in Beijing, Anhui and Malaysia but different to that from Australia. A point mutation was present in the amino acid sequence of the VP1 gene.

Matched MeSH terms: Hand, Foot and Mouth Disease

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