The emergence and spread of one Coxsackievirus A16 Genogroup D novel recombinant strain that caused a clustering HFMD outbreak in Shanghai, China, 2016.
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ABSTRACT:
SUBMITTER: Wang J
PROVIDER: S-EPMC6052075 | biostudies-literature | 2018 Jul
REPOSITORIES: biostudies-literature
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The emergence and spread of one Coxsackievirus A16 Genogroup D novel recombinant strain that caused a clustering HFMD outbreak in Shanghai, China, 2016.
Wang Jiayu J Teng Zheng Z Chu Wei W Fang Fanghao F Cui Xiaoqing X Guo Xiaokui X Zhang Xi X Thorley Bruce R BR Zhu Yongzhang Y
Emerging microbes & infections 20180718 1
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Project description:Coxsackievirus A16 (CV-A16; Picornaviridae) is an enterovirus (EV) type associated with hand, foot, and mouth disease (HFMD) in children. To investigate the spatial spread of CV-A16, we used viral sequence data sampled during a prospective sentinel surveillance of HFMD in France (2010 to 2014) and phylogenetic reconstruction. A data set of 168 VP1 sequences was assembled with 416 publicly available sequences of various geographic origins. The CV-A16 sequences reported were assigned to two clades, genogroup B and a previously uncharacterized clade D. The time origins of clades B and D were assessed in 1978 (1973 to 1981) and 2004 (2001 to 2007), respectively. The shape of the global CV-A16 phylogeny indicated worldwide cocirculation of genetically distinct virus lineages over time and across geographic regions. Phylogenetic tree topologies and Bayes factor analysis indicated virus migration. Virus transportation events in clade B within Europe and Asia and between countries of the two geographic regions were assessed. The sustained transmission of clade D viruses over 4 years was analyzed at the township level in France and traced back to Peru in South America. Comparative genomics provided evidence of recombination between CV-A16 clades B and D and suggested an intertype recombinant origin for clade D. Time-resolved phylogenies and HFMD surveillance data indicated that CV-A16 persistence is sustained by continuing virus migration at different geographic scales, from community transmission to virus transportation between distant countries. The results showed a significant impact of virus movements on the epidemiological dynamics of HFMD that could have implications for disease prevention.IMPORTANCE Coxsackievirus A16 is one of the most prevalent enterovirus types in hand, foot, and mouth disease outbreaks reported in Southeast Asia. This study is based on epidemiological and viral data on HFMD caused by CV-A16 in a European country. The phylogeographic data complemented the syndromic surveillance with virus migration patterns between geographic regions in France. The results show how viral evolutionary dynamics and global virus spread interact to shape the worldwide pattern of an EV disease. CV-A16 transmission is driven by movements of infected individuals at different geographic levels: within a country (local dynamics), between neighboring countries (regional dynamics), and between distant countries (transcontinental dynamics). The results are consistent with our earlier data on EV-A71 and confirm the epidemiological interconnection of Asia and Europe with regard to EV infections.
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Project description:Introduction: Hand, foot, and mouth disease (HFMD) is a mild self-limited childhood infectious disease caused by a variety of enteroviruses (EVs). Aim: To investigate the molecular epidemiology of EVs associated with HFMD and their clinical presentation during the HFMD outbreak that occurred in the Jenin district, Palestine, from May to August 2024. Materials and Methods: Forty-four (44) throat and vesicular swabs were tested for enteroviral infections using two RT-PCR assays targeting both the 5'NTR and the VP1-2A regions of the enteroviral genome for the diagnosis and genotyping. Patients' demographic data and clinical history were used to create an epidemiological curve. EpiInfo free software was used to draw a cluster mapping. MEGA-X was used to construct a maximum likelihood (ML) tree. PopArt 1.7 software was used to construct neighbor-joining network. Results: The mean age of the study sample was 2.08 (0.25-12 years) with 95% (42/44) under five years old. The male/female ratio was 0.9. All cases presented with typical HFMD signs and symptoms with variable sites of signs. Of the 44 samples, 36 yield positive RT-PCR targeting the 5'NTR. Seven randomly selected positive RT-PCR-5'NTR samples were sequenced using Sanger sequencing for genotyping. It was shown that all were CV-A16 sub-genogroup B1c. Phylogenetic analysis of VP1-2A region sequences showed that all Palestinian CV-A16 isolates form a pure haplogroup of CV-A16 sub-genotype B1c. Furthermore, although haplotype network analysis showed high variation between the viral sequences, the haplotype analysis supported the ML phylogenetic tree in having them all in one haplogroup. Conclusion: CV-A16, sub-genotype B1c was the virus responsible for the HFMD outbreak in the Jenin district of Palestine in the summer of 2024. Phylogenetic and haplotype analysis showed that CV-A16 strains cluster closely with each other and very close to an Indian isolate (OR437338.1), indicating the monomorphic nature of this strain with low genetic variation and the probability of virus importation.
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Project description:Human enteroviruses (HEV) have been linked to hand, foot, and mouth disease (HFMD) in the Pacific and Southeast Asia for decades. Many cases of HFMD have been attributed to coxsackievirus A16 (CV-A16, CA16), based on only partial viral genome determination. Viral phenotypes are also poorly defined. Herein, we have genetically and phenotypically characterized multiple circulating CV-A16 viruses from HFMD patients and determined multiple full-length sequences of these circulating viruses. We discovered that the circulating CV-A16 viruses from HFMD patients are genetically distinct from the proto-type CV-A16 G10. We have also isolated circulating CV-A16 viruses from hospitalized HFMD patients and compared their virological differences. Interestingly, circulating CV-A16 viruses are more pathogenic in a neonatal mouse model than is CV-A16 G10. Thus, we have found circulating recombinant forms of CV-A16 (CRF CV-A16) that are related to, but different from, the prototype CV-A16 G10 that have distinct biological phenotypes.
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Project description:Coxsackievirus A10 (CVA10) is one of the major causative agents of hand, foot and mouth disease (HFMD). To investigate the epidemiological characteristics as well as genetic features of CVA10 currently circulating in Shanghai, China, we collected a total of 9,952 sporadic HFMD cases from January 2016 to December 2020. In the past five years, CVA10 was the fourth prevalent causatives associated with HFMD in Shanghai and the overall positive rate was 2.78%. The annual distribution experienced significant fluctuations over the past five years. In addition to entire VP1 sequencing, complete genome sequencing and recombination analysis of CVA10 isolates in Shanghai were further performed. A total of 64 near complete genomes and 11 entire VP1 sequences in this study combined with reference sequences publicly available were integrated into phylogenetic analysis. The CVA10 sequences in this study mainly belonged to genogroup C and presented 91%-100% nucleotide identity with other Chinese isolates based on VP1 region. For the first time, our study reported the appearance of CVA10 genogroup D in Chinese mainland, which had led to large-scale outbreaks in Europe previously. The recombination analysis showed the recombination break point located between 5,100 nt and 6,700 nt, which suggesting intertypic recombination with CVA16 genogroup D. To conclusion, CVA10 genogroup C was the predominant genogroup in Shanghai during 2016-2020. CVA10 recombinant genogroup D was firstly reported in circulating in Chinese mainland. Continuous surveillance is needed to better understand the evolution relationships and transmission pathways of CVA10 to help to guide disease control and prevention.
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Project description:Coxsackievirus-A6 (CV-A6) is responsible for more severe dermatological manifestations compared to other enteroviruses such as CV-A10, CV-A16, and EV-A71, causing HFMD in children and adults. Between 2005 and 2007, the recombinant subclade D3/RF-A started to expand globally, and a CV-A6 pandemic started. The study aimed to conduct whole-genome sequencing (WGS) of an isolated CV-A6 strain from currently circulating HFMD cases from India in 2022. Gene-specific RT-PCR and sequencing were used to perform molecular characterization of the isolated virus. Confirmation of these isolates was also performed by transmission electron microscopy and WGS. Among eleven positive clinical enterovirus specimens, eight CV-A6 strains were successfully isolated in the RD cell line. Isolates confirmed the presence of the CV-A6 strain based on VP1 and VP2 gene-specific RT-PCR. Sequences of isolates were clustered and identified as the novel CV-A6 strain of the D3/Y sub-genotype in India. The studies revealed that the D3/Y sub-genotype is being introduced into Indian circulation. The predicted putative functional loops found in VP1 of CV-A6 showed that the nucleotide sequences of the amino acid were a remarkably conserved loop prediction compatible with neutralizing linear epitopes. Therefore, this strain represents a potential candidate for vaccine development and antiviral studies.
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Project description:Hand, foot and mouth disease (HFMD) is a common childhood infectious disease, caused by enteroviruses (EVs), which can present with typical or atypical lesions. The illness is self-limiting, but it can also have serious complications. Since 1997, HFMD infections have become endemic and have increased to epidemic proportions across the Asia Pacific region, including India. Coxsackievirus-A16 (CV-A16) outbreaks occurred in India from 2005 onwards, although the clinical symptoms were noticeably different during this period. Understanding the population dynamics of enteroviruses that cause HFMD is crucial in the post-polio era because one of the circulating strain may replace another as the dominant strain. The aim of this study is to describe the genetic features of the CV-A16 strains isolated from hand, foot and mouth disease (HFMD) patients in India. Reverse transcription PCR (RT-PCR) and cell-culture-based isolation of CV-A16 was done from the 55 clinical samples. The entire genome of the CV-A16 isolate was performed from the seven isolates. After the sequences were analysed, a phylogenetic tree was created using bioinformatics tools. The total genomic length obtained was 7411 base pairs (bp). Nucleotide similarity across various regions, including 5'UTR, P1, P2 and 3'UTR, ranged from 87.0-97.9 %, 77.0-95.4 %, 80.3-96.9 %, and 77.9-96.2 %, respectively. Correspondingly, similarities in the VP1 region's nucleotide and amino acid sequences were 91.4-96.4 % and 99.3-99.7 %, respectively. Phylogenetic analysis highlighted that CV-A16 strains identified in Pune, Maharashtra, were grouped within the same cluster. The analysed CV-A16 isolates in this study aligned with subgenotype B1c. These findings have far-reaching implications for the surveillance, prevention and management of HFMD and CV-A16. Monitoring the dynamics of CV-A16 strains, informed by the genetic characteristics identified here, will significantly impact strategies aimed at tackling HFMD and its associated public health challenges.
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Project description:Coxsackievirus A16 Genome sequencing and assembly
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