scholarly journals RSAD2 and AIM2 Modulate Coxsackievirus A16 and Enterovirus A71 Replication in Neuronal Cells in Different Ways That May Be Associated with Their 5′ Nontranslated Regions

2017 ◽  
Vol 92 (6) ◽  
Author(s):  
Thinesshwary Yogarajah ◽  
Kien Chai Ong ◽  
David Perera ◽  
Kum Thong Wong
Keyword(s):  
Viral Replication ◽  
Neuronal Cells ◽  
Neuroblastoma Cells ◽  
Foot And Mouth Disease ◽  
Neurological Complications ◽  
Mouth Disease ◽  
Host Responses ◽  
Coxsackievirus A16 ◽  
Enterovirus A71 ◽  
Foot And Mouth

ABSTRACT Coxsackievirus A16 (CV-A16) and enterovirus A71 (EV-A71) are closely related enteroviruses that cause the same hand, foot, and mouth disease (HFMD), but neurological complications occur only very rarely in CV-A16 compared to EV-A71 infections. To elucidate host responses that may be able to explain these differences, we performed transcriptomic analysis and real-time quantitative PCR (RT-qPCR) in CV-A16-infected neuroblastoma cells (SK-N-SH), and the results showed that the radical S -adenosylmethionine domain containing 2 (RSAD2) was the highest upregulated gene in the antimicrobial pathway. Increased RSAD2 expression was correlated with reduced viral replication, while RSAD2 knockdown cells were correlated with increased replication. EV-A71 replication showed no apparent correlation to RSAD2 expressions. Absent in melanoma 2 (AIM2), which is associated with pyroptotic cell death, was upregulated in EV-A71-infected neurons but not in CV-A16 infection, suggesting that the AIM2 inflammasome played a significant role in suppressing EV-A71 replication. Chimeric viruses derived from CV-A16 and EV-A71 but containing swapped 5′ nontranslated regions (5′ NTRs) showed that RSAD2 expression/viral replication and AIM2 expression/viral replication patterns may be linked to the 5′ NTRs of parental viruses. Differences in secondary structure of internal ribosomal entry sites within the 5′ NTR may be responsible for these findings. Overall, our results suggest that CV-A16 and EV-A71 elicit different host responses to infection, which may help explain the apparent lower incidence of CV-A16-associated neurovirulence in HFMD outbreaks compared to EV-A71 infection. IMPORTANCE Although coxsackievirus A16 (CV-A16) and enterovirus A17 (EV-A71) both cause hand, foot, and mouth disease, EV-A71 has emerged as a leading cause of nonpolio, enteroviral fatal encephalomyelitis among young children. The significance of our research is in the identification of the possible differing and novel mechanisms of CV-A16 and EV-A71 inhibition in neuronal cells that may impact viral neuropathogenesis. We further showed that viral 5′ NTRs may play significant roles in eliciting different host response mechanisms.

scholarly journals Longitudinal study on enterovirus A71 and coxsackievirus A16 genotype/subgenotype replacements in hand, foot and mouth disease patients in Thailand, 2000–2017

2019 ◽  
Vol 80 ◽  
pp. 84-91 ◽  
Author(s):  
Pirom Noisumdaeng ◽  
Achareeya Korkusol ◽  
Jarunee Prasertsopon ◽  
Kantima Sangsiriwut ◽  
Kulkanya Chokephaibulkit ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Coxsackievirus A16 ◽  
Enterovirus A71 ◽  
Foot And Mouth

scholarly journals First isolation and genomic characterization of enterovirus A71 and coxsackievirus A16 from hand foot and mouth disease patients in the Lao PDR

2014 ◽  
Vol 2 (6) ◽  
pp. 170-172 ◽  
Author(s):  
V.H. Nguyen ◽  
B. Sibounheuang ◽  
K. Phommasone ◽  
M. Vongsouvath ◽  
P.N. Newton ◽  
...  
Keyword(s):  
Lao Pdr ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Coxsackievirus A16 ◽  
Enterovirus A71 ◽  
Foot And Mouth ◽  
Genomic Characterization

scholarly journals A large-scale outbreak of hand, foot and mouth disease, France, as at 28 September 2021

2021 ◽  
Vol 26 (43) ◽  
Author(s):  
Audrey Mirand ◽  
Robert Cohen ◽  
Maxime Bisseux ◽  
Stéphanie Tomba ◽  
Fabienne Cahn Sellem ◽  
...  
Keyword(s):  
Early Detection ◽  
Large Scale ◽  
Foot And Mouth Disease ◽  
Neurological Complications ◽  
Mouth Disease ◽  
Clinical Samples ◽  
Enterovirus A71 ◽  
Foot And Mouth ◽  
Virological Surveillance

We report a large-scale outbreak of hand, foot and mouth disease (HFMD) in France. As at 28 September 2021, 3,403 cases have been reported (47% higher than in 2018–19). We prospectively analysed 210 clinical samples; 190 (90.5%) were enterovirus-positive. Most children presented with atypical HFMD. Coxsackievirus (CV)A6 (49.5%; 94/190) was predominant; no enterovirus A71 was detected. Dermatological and neurological complications of HFMD justify prospective syndromic and virological surveillance for early detection of HFMD outbreaks and identification of associated types.

scholarly journals Epidemical and etiological study on hand, foot and mouth disease following EV-A71 vaccination in Xiangyang, China

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiao-Dan Meng ◽  
Yeqing Tong ◽  
Zhen-Ni Wei ◽  
Lei Wang ◽  
Jian-Yi Mai ◽  
...  
Keyword(s):  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Conventional Pcr ◽  
Coxsackievirus A16 ◽  
Enterovirus A71 ◽  
Coxsackievirus A6 ◽  
Foot And Mouth ◽  
Etiological Spectrum ◽  
Etiological Study ◽  
Infants And Young Children

AbstractCoxsackievirus A6 (CV-A6) and Coxsackievirus A10 (CV-A10) have been emerging as the prevailing serotypes and overtaking Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) in most areas as main pathogens of hand, foot and mouth disease (HFMD) in China since 2013. To investigate whole etiological spectrum following EV-A71 vaccination of approximate 40,000 infants and young children in Xiangyang, enteroviruses were serotyped in 4415 HFMD cases from October 2016 to December 2017 using Real Time and conventional PCR and cell cultures. Of the typeable 3201 specimen, CV-A6 was the predominant serotype followed by CV-A16, CV-A10, CV-A5, CV-A2 and EV-A71 with proportions of 59.54%, 15.31%, 11.56%, 4.56%, 3.78% and 3.03%, respectively. Other 12 minor serotypes were also detected. The results demonstrated that six major serotypes of enteroviruses were co-circulating, including newly emerged CV-A2 and CV-A5. A dramatic decrease of EV-A71 cases was observed, whereas the total cases remained high. Multivalent vaccines against major serotypes are urgently needed for control of HFMD.

scholarly journals Hand, Foot, and Mouth Disease Caused by Coxsackievirus A6: A Preliminary Report from Istanbul

2019 ◽  
Vol 68 (2) ◽  
pp. 165-171
Author(s):  
AYSE N. CEYLAN ◽  
OZDEN TUREL ◽  
BILGE SUMBUL GULTEPE ◽  
ELIF INAN ◽  
AYSEL VEHAPOGLU TURKMEN ◽  
...  
Keyword(s):  
Preliminary Report ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Rt Pcr ◽  
Coxsackievirus A16 ◽  
Specific Primers ◽  
Enterovirus A71 ◽  
Coxsackievirus A6 ◽  
The World ◽  
Foot And Mouth

Hand, foot, and mouth disease (HFMD) is caused by various serotypes of Enterovirus genus. Coxsackievirus A16 (CV-A16) and enterovirus A71 (EV-A71) were known to be the only responsible agents for these epidemics; however, this opinion was challenged after the detection that coxsackievirus A6 (CV-A6) was the responsible species for the outbreak in Finland in 2008. HFMD is frequently seen in Turkey, and no detailed study on its clinical and microbiological epidemiology has previously been reported. The present study addresses this question. Twenty-seven patient samples collected between 2015 and 2017 were included in the study. Typing was conducted by RT-PCR and the sequencing applied directly to patient’s samples and as well as to the viral cultures with pan-enterovirus and serotype-specific primers. The presence of Enterovirus in 12 of 27 HFMD samples was shown with RT-PCR. The causative agent for three of these 12 samples was CV-A16, one of the most frequent two serotypes around the world, and the remaining nine samples was CV-A6. The findings of the study are relevant since it pertains to the molecular epidemiology of HFMD in Turkey, a gateway country where different serotypes might be circulating and transmitted. The findings also support the notion that CV-A6 cases are rising in number, which has caused more severe clinical features and widespread rashes in recent outbreaks.

Virulence of enterovirus-A71 fluctuates depending on the phylogenetic clade formed in the epidemic year and epidemic region

2021 ◽  
Author(s):  
Kyousuke Kobayashi ◽  
Hidekazu Nishimura ◽  
Katsumi Mizuta ◽  
Tomoha Nishizawa ◽  
Son T. Chu ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Foot And Mouth Disease ◽  
Virus Genome ◽  
Mouth Disease ◽  
Asia Pacific ◽  
Enterovirus A71 ◽  
Viral Virulence ◽  
Foot And Mouth ◽  
Potential Risks ◽  
A Minor

Although epidemics of hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) have occurred worldwide, the Asia-Pacific region has seen large sporadic outbreaks with many severe neurological cases. This suggests that the virulence of the circulating viruses fluctuates in each epidemic and that HFMD outbreaks with many severe cases occur when highly virulent viruses are circulating predominantly, which has not been experimentally verified. Here, we analyzed 32 clinically isolated strains obtained in Japan from 2002 to 2013, along with 27 Vietnamese strains obtained from 2015 to 2016 that we characterized previously using human SCARB2 transgenic mice. Phylogenetic analysis of the P1 region classified them into five clades belonging to subgenogroup B5 (B5-I to B5-V) and five clades belonging to subgenogroup C4 (C4-I to C4-V) according to the epidemic year and region. Interestingly, the clade B5-I and B5-II were very virulent, while clades B5-III, B5-IV, and B5-V were less virulent. Clades C4-II, C4-III, C4-IV, and C4-V were virulent, while clade C4-I was not. The result experimentally showed for the first time that several clades with different virulence levels emerged one after another. The experimental virulence evaluation of circulating viruses using SCARB2 transgenic mice is helpful to assess potential risks of circulating viruses. These results also suggest that a minor nucleotide or amino acid substitution in the EV-A71 genome during circulation may cause fluctuations in virulence. The data presented herein may increase our understanding of the dynamics of viral virulence during epidemics. IMPORTANCE Outbreaks of hand, foot, and mouth disease (HFMD) with severe enterovirus A71 (EV-A71) cases have occurred repeatedly, mainly in Asia. In severe cases, central nervous system complications can lead to death, making it an infectious disease of importance to public health. An unanswered question about this disease is why outbreaks of HFMD with many severe cases sometimes occur. Here, we collected EV-A71 strains that were prevalent in Japan and Vietnam over the past 20 years and evaluated their virulence in a mouse model of EV-A71 infection. This method clearly revealed that viruses belonging to different clades have different virulence, indicating that the method is powerful to assess the potential risks of the circulating viruses. The results also suggested that factors in the virus genome may potentially cause an outbreak with many severe cases and that further studies may facilitate the prediction of large epidemics of EV-A71 in the future.

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