Dataset Information

The emerging sub-genotype C2 of CoxsackievirusA10 Associated with Hand, Foot and Mouth Disease extensively circulating in mainland of China.

ABSTRACT: Coxsackievirus A10 (CV-A10) associated with Hand, foot, and mouth disease (HFMD) cases emerged increasingly in recent years. In this study, the samples from nation-wide HFMD surveillance, including 27 out of 31 provinces in China were investigated, and the continuous and extensive virological surveillance, covered 13 years, were conducted to provide a comprehensive molecular characterization analysis of CV-A10. 855 CV-A10 viruses (33 severe cases included), were isolated from HFMD children patients during 2009 to 2016 in China. 164 representative sequences from these viruses, together with 117 CV-A10 sequences downloaded from GenBank based on entire VP1 were recruited in this study. Two new genotypes (F and G) and two sub-genotypes (C1 and C2) were identified. Among 264 Chinese sequences, 9 of them were genotype B, 8 of them were C1, and the other (247) were C2, the predominant sub-genotype in China since 2012. Chinese C2 viruses showed obvious temporal characteristics and can be divided into 3 clusters (cluster 1~3). Cluster 3 viruses was circulating extensively during 2014 and 2016 with more severe cases. It is very necessary and important to continuously conduct the extensive virological surveillance for CV-A10, and further evolutionary studies will provide more evidence on its evolution and virulence.

SUBMITTER: Ji T

PROVIDER: S-EPMC6127217 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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The emerging sub-genotype C2 of CoxsackievirusA10 Associated with Hand, Foot and Mouth Disease extensively circulating in mainland of China.

Ji Tianjiao T Guo Yue Y Huang Wei W Shi Yong Y Xu Yi Y Tong Wenbin W Yao Wenqing W Tan Zhaolin Z Zeng Hanri H Ma Jiangtao J Zhao Hua H Han Taoli T Zhang Yong Y Yan Dongmei D Yang Qian Q Zhu Shuangli S Zhang Yan Y Xu Wenbo W

Scientific reports 20180906 1

Coxsackievirus A10 (CV-A10) associated with Hand, foot, and mouth disease (HFMD) cases emerged increasingly in recent years. In this study, the samples from nation-wide HFMD surveillance, including 27 out of 31 provinces in China were investigated, and the continuous and extensive virological surveillance, covered 13 years, were conducted to provide a comprehensive molecular characterization analysis of CV-A10. 855 CV-A10 viruses (33 severe cases included), were isolated from HFMD children patie ...[more]

PMID: 30190558

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Project description:Coxsackievirus A6 (CV-A6) is an emerging pathogen associated with hand, foot, and mouth disease (HFMD). Its genetic characterization and pathogenic properties are largely unknown. Here, we report 39 circulating CV-A6 strains isolated in 2013 from HFMD patients in northeast China. Three major clusters of CV-A6 were identified and related to CV-A6, mostly from Shanghai, indicating that domestic CV-A6 strains were responsible for HFMD emerging in northeast China. Four full-length CV-A6 genomes representing each cluster were sequenced and analyzed further. Bootscanning tests indicated that all four CV-A6-Changchun strains were most likely recombinants between the CV-A6 prototype Gdula and prototype CV-A4 or CV-A4-related viruses, while the recombination pattern was related to, yet distinct from, the strains isolated from other regions of China. Furthermore, different CV-A6 strains showed different capabilities of viral replication, release, and pathogenesis in a mouse model. Further analyses indicated that viral protein 2C contributed to the diverse pathogenic abilities of CV-A6 by causing autophagy and inducing cell death. To our knowledge, this study is the first to report lethal and nonlethal strains of CV-A6 associated with HFMD. The 2C protein region may play a key role in the pathogenicity of CV-A6 strains.IMPORTANCE Hand, foot, and mouth disease (HFMD) is a major and persistent threat to infants and children. Besides the most common pathogens, such as enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16), other enteroviruses are increasingly contributing to HFMD. The present study focused on the recently emerged CV-A6 strain. We found that CV-A6 strains isolated in Changchun City in northeast China were associated with domestic origins. These Changchun viruses were novel recombinants of the CV-A6 prototype Gdula and CV-A4. Our results imply that measures to control CV-A6 transmission are urgently needed. Further analyses revealed differing pathogenicities in strains isolated in a neonatal mouse model. One of the possible causes has been narrowed down to the viral protein 2C, using phylogenetic studies, viral sequences, and direct tests on cultured human cells. Thus, the viral 2C protein is a promising target for antiviral drugs to prevent CV-A6-induced tissue damage.

Project description:BackgroundSevere hand-foot-and-mouth disease (HFMD) is a life-threatening contagious disease among young children and infants. Although enterovirus A71 has been well acknowledged to be the dominant cause of severe HFMD, there still remain other unidentified risk factors for severe HFMD. Previous studies mainly focused on identifying the individual-level risk factors from a clinical perspective, while rare studies aimed to clarify the association between regional-level risk factors and severe HFMD, which may be more important from a public health perspective.MethodsWe retrieved the clinical HFMD counts between 2008 and 2014 from the Chinese Center for Disease Control and Prevention, which were used to calculated the case-severity rate in 143 prefectural-level cities in mainland China. For each of those 143 cities, we further obtained city-specific characteristics from the China City Statistical Yearbook (social and economic variables) and the national meteorological monitoring system (meteorological variables). A Poisson regression model was then used to estimate the associations between city-specific characteristics (reduced by the principal component analysis to avoid multicollinearity) and the case-severity rate of HFMD. The above analysis was further stratified by age and gender to examine potential modifying effects and vulnerable sub-populations.ResultsWe found that the case-severity rate of HFMD varied dramatically between cities, ranging from 0 to 8.09%. Cities with high case-severity rates were mainly clustered in Central China. By relating the case-severity rate to city-specific characteristics, we found that both the principal component characterized by a high level of social and economic development (RR = 0.823, 95%CI 0.739, 0.916) and another that characterized by warm and humid climate (RR = 0.771, 95%CI 0.619, 0.960) were negatively associated with the case-severity rate of HFMD. These estimations were consistent across age and gender sub-populations.ConclusionExcept for the type of infected pathogen, the case-severity rate of HFMD was closely related to city development and meteorological factor. These findings suggest that social and environmental factors may also play an important role in the progress of severe HFMD.

Project description:There is limited evidence about the association between ambient temperature and the incidence of pediatric hand, foot, and mouth disease (HFMD) nationwide in China.We examined the childhood temperature-HFMD associations across mainland China, and we projected the change in HFMD cases due to projected temperature change by the 2090s.Data on daily HFMD (children 0-14 y old) counts and weather were collected from 362 sites during 2009-2014. Daily temperature by the 2090s was downscaled under the Representative Concentration Pathway (RCP) 4.5 and 8.5 scenarios. Temperature-HFMD associations were quantified using a two-stage Poisson regression with a distributed lag nonlinear model. The impact of changes in temperature on the incidence of HFMD was estimated by combining the fitted temperature-HFMD associations with projected temperatures under each scenario, assuming a constant population structure. Sensitivity analyses were performed to assess the influence of primary model assumptions.During 2009-2014, >11 million HFMD cases were reported. In most regions, the temperature-HFMD association had an inverted U shape with a peak at approximately 20°C, but the association leveled off or continued to increase in the Inner Mongolia and Northeast regions. When estimates were pooled across all regions and the population size was held constant, the projected incidence of HFMD increased by 3.2% [95% empirical confidence interval (eCI): ?13.5%, 20.0%] and 5.3% (95% eCI: ?33.3%, 44.0%) by the 2090s under the RCP 4.5 and 8.5 scenarios, respectively. However, regional projections suggest that HFMD may decrease with climate change in temperate areas of central and eastern China.Our estimates suggest that the association between temperature and HFMD varies across China and that the future impact of climate change on HFMD incidence will vary as well. Other factors, including changes in the size of the population at risk (children 0-14 y old) will also influence future HFMD trends. https://doi.org/10.1289/EHP3062.

Dataset Information

The emerging sub-genotype C2 of CoxsackievirusA10 Associated with Hand, Foot and Mouth Disease extensively circulating in mainland of China.

Publications

The emerging sub-genotype C2 of CoxsackievirusA10 Associated with Hand, Foot and Mouth Disease extensively circulating in mainland of China.

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