Genome Analysis of Coxsackievirus A4 Isolates From Hand, Foot, and Mouth Disease Cases in Shandong, China

Wang, Min; Li, Juan; Yao, Mingxiao; Zhang, Yawei; Hu, Tao; Carr, Michael J.; Duchêne, Sebastián; Zhang, Xing-Cheng; Zhang, Zhenjie; Zhou, Hong; Tong, Yigang; Ding, Shujun; Wang, Xianjun; Shi, Weifeng

doi:10.3389/fmicb.2019.01001

Cited by 16 publications

(20 citation statements)

References 49 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have shown that mutations in structural proteins have an effect on virulence and pathogenicity. Even one amino acid change in structural proteins may modulate important functions in virus infection [ 67 , 68 , 69 , 70 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Adaptation of Coxsackievirus B1 during Persistent Infection in Pancreatic Cells

et al. 2020

View full text Add to dashboard Cite

Coxsackie B (CVB) viruses have been associated with type 1 diabetes. We have recently observed that CVB1 was linked to the initiation of the autoimmune process leading to type 1 diabetes in Finnish children. Viral persistency in the pancreas is currently considered as one possible mechanism. In the current study persistent infection was established in pancreatic ductal and beta cell lines (PANC-1 and 1.1B4) using four different CVB1 strains, including the prototype strain and three clinical isolates. We sequenced 5′ untranslated region (UTR) and regions coding for structural and non-structural proteins and the second single open reading frame (ORF) protein of all persisting CVB1 strains using next generation sequencing to identify mutations that are common for all of these strains. One mutation, K257R in VP1, was found from all persisting CVB1 strains. The mutations were mainly accumulated in viral structural proteins, especially at BC, DE, EF loops and C-terminus of viral capsid protein 1 (VP1), the puff region of VP2, the knob region of VP3 and infection-enhancing epitope of VP4. This showed that the capsid region of the viruses sustains various changes during persistency some of which could be hallmark(s) of persistency.

show abstract

Section: Discussionmentioning

confidence: 99%

Genetic Adaptation of Coxsackievirus B1 during Persistent Infection in Pancreatic Cells

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Prior to 2009, viral pathogens associated with HFMD included enterovirus A71 (EVA71) and CVA16; however, in recent years, other types of enteroviruses (EVs), such as CVA4, CVA6 and CVA10 have increased in prevalence [2–3]. Numerous outbreaks of CVA4 have occurred during recent years in different regions in China, such as Fujian [4], Shandong [5, 6], Sichuan [7], Yunnan [8], and Jiangsu [9]. Other countries, such as Thailand [2, 10], Australia [11] and Italy [12] have also reported CVA4 infections.…”

Section: Introductionmentioning

confidence: 99%

A neonatal murine model of coxsackievirus A4 infection for evaluation of vaccines and antiviral drugs

Zhang

Carr

et al. 2019

Emerging Microbes & Infections

Self Cite

View full text Add to dashboard Cite

Coxsackievirus A4 (CVA4) infection can cause hand, foot and mouth disease (HFMD), an epidemic illness affecting neonatal and paediatric cohorts, which can develop to severe neurological disease with high mortality. In this study, we established the first ICR mouse model of CVA4 infection for the evaluation of inactivated vaccines and antiviral drug screening. The CVA4 YT226R strain was selected to infect the neonatal mice and three infectious factors were optimized to establish the infection model. The 3-day-old neonatal mice exhibited clinical symptoms such as hind limb paralysis and death. The severe inflammatory reactions were closely related to the abnormal expression of the acute phase response proinflammatory cytokine IL-6 and an imbalance in the IFN-γ/IL-4 ratio. Importantly, the inactivated CVA4 whole-virus vaccine induced humoral immune responses in adult females and the maternal antibodies afforded mice complete protection against lethal dose challenges of homologous or heterologous CVA4 strains. Both IFN-α2a and antiserum inhibited the replication of CVA4 and increased the survival rates of neonatal mice during the early stages of infection. This neonatal murine model of CVA4 infection will be useful for the development of prophylactic and therapeutic vaccines and for screening of antiviral drugs targeting CVA4 to decrease morbidity and mortality.

show abstract

“…When using the neighbor-joining, minimum evolution and an UPGMA methods, the phylogenetic trees all formed almost the same topologies as the ML tree ( Supplementary Figure S1 ). This finding is rare among enteroviruses, as the prototype strain is always the most divergent strain among the genotyping results [ 3 , 4 , 5 , 6 , 7 , 8 ]. The 24 Chinese strains fell into the three genotypes, C, D and E, suggesting that the circulation of CV-A8 in China had distinctive evolutionary routes.…”

Section: Resultsmentioning

confidence: 99%

“…Phylogenetic trees based on the complete VP1 capsid sequences of EVs have been used for discrimination of genotypes, as the VP1 region is surface exposed, contains many important neutralisation epitopes and is serotype specific. Based on this approach, several EV serotypes, such as EV-A71, CV-A16, CV-A6, CV-A4, and CV-A2, have been genotyped [ 3 , 4 , 5 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic Diversity Analysis of Coxsackievirus A8 Circulating in China and Worldwide Reveals a Highly Divergent Genotype

Song¹,

Wang²,

Zhang³

et al. 2020

Viruses

View full text Add to dashboard Cite

Coxsackievirus A8 (CV-A8) is one of the pathogens associated with hand, foot and mouth disease (HFMD) and herpangina (HA), occasionally leading to severe neurological disorders such as acute flaccid paralysis (AFP). Only one study aimed at CV-A8 has been published to date, and only 12 whole-genome sequences are publicly available. In this study, complete genome sequences from 11 CV-A8 strains isolated from HFMD patients in extensive regions from China between 2013 and 2018 were determined, and all sequences from GenBank were retrieved. A phylogenetic analysis based on a total of 34 complete VP1 sequences of CV-A8 revealed five genotypes: A, B, C, D and E. The newly emerging genotype E presented a highly phylogenetic divergence compared with the other genotypes and was composed of the majority of the strains sequenced in this study. Markov chain Monte Carlo (MCMC) analysis revealed that genotype E has been evolving for nearly a century and somehow arose in approximately 2010. The Bayesian skyline plot showed that the population size of CV-A8 has experienced three dynamic fluctuations since 2001. Amino acid residues of VP1100N, 103Y, 240T and 241V, which were embedded in the potential capsid loops of genotype E, might enhance genotype E adaption to the human hosts. The CV-A8 whole genomes displayed significant intra-genotypic genetic diversity in the non-capsid region, and a total of six recombinant lineages were detected. The Chinese viruses from genotype E might have emerged recently from recombining with European CV-A6 strains. CV-A8 is a less important HFMD pathogen, and the capsid gene diversity and non-capsid recombination variety observed in CV-A8 strains indicated that the constant generation of deleterious genomes and a constant selection pressure against these deleterious mutations is still ongoing within CV-A8 quasispecies. It is possible that CV-A8 could become an important pathogen in the HFMD spectrum in the future. Further surveillance of CV-A8 is greatly needed.

show abstract

Genome Analysis of Coxsackievirus A4 Isolates From Hand, Foot, and Mouth Disease Cases in Shandong, China

Cited by 16 publications

References 49 publications

Genetic Adaptation of Coxsackievirus B1 during Persistent Infection in Pancreatic Cells

Genetic Adaptation of Coxsackievirus B1 during Persistent Infection in Pancreatic Cells

A neonatal murine model of coxsackievirus A4 infection for evaluation of vaccines and antiviral drugs

Genetic Diversity Analysis of Coxsackievirus A8 Circulating in China and Worldwide Reveals a Highly Divergent Genotype

Contact Info

Product

Resources

About