Abstract:Background: Hand, foot and mouth disease (HFMD) is usually caused by EVA71 and CVA16 except for a few cases that are caused by non-EVA71 non-CAV16 enteroviruses. Coxsackievirus B3 (CVB3) is mostly associated with myocarditis, occasionally with HFMD. Methods: The partial VP1 gene of enteroviruses were amplified and sequenced from 610 throat swabs from clinically confirmed HFMD children. All available CVB3 near full-length genomic and VP1 sequences were downloaded from GenBank. Phylogenetic and distance analyses… Show more
“…To date, CVB3 strains are associated with various diseases, and the manifestations vary from mild respiratory [ 33 ], gastrointestinal infections [ 34 , 35 ], herpangina [ 36 ], and hand, foot, and mouth disease [ 7 , 8 , 37 ], to more severe diseases such as heart disease (including viral myocarditis [ 6 , 38 ], pericarditis [ 39 ], and acute myocardial infarction [ 40 ]), CNS involvement (meningitis [ 30 , 36 , 41 – 43 ], meningo-cerebellitis [ 11 ], encephalitis [ 44 ], and AFP [ 45 – 47 ]), and pancreatic interrelated disease (pancreatitis [ 48 ], diabetes [ 49 ]). More seriously, the virus can cause neonatal sepsis-like illness and sudden death in infected infants [ 38 , 50 ] and adults with low immune function.…”
Section: Resultsmentioning
confidence: 99%
“…Coxsackievirus B3 (CVB3) was first reported in Connecticut, the USA in 1949, and has emerged as an active pathogen in myocarditis [ 6 ], aseptic meningitis (AM), HFMD [ 7 , 8 ], and pancreatitis [ 9 ], causing a heavy burden on society. CVB3 infection is the most common cause of viral myocarditis, characterized by viral infection and myocardial inflammation [ 10 , 11 ].…”
Background
Coxsackievirus B3 (CVB3) has emerged as an active pathogen in myocarditis, aseptic meningitis, hand, foot, and mouth disease (HFMD), and pancreatitis, and is a heavy burden on public health. However, CVB3 has not been systematically analyzed with regard to whole-genome diversity and recombination. Therefore, this study was undertaken to systematically examine the genetic characteristics of CVB3 based on its whole genome.
Methods
We combined CVB3 isolates from our national HFMD surveillance and global sequences retrieved from GenBank. Phylogenetic analysis was performed to examine the whole genome variety and recombination forms of CVB3 in China and worldwide.
Results
Phylogenetic analysis showed that CVB3 strains isolated worldwide could be classified into clusters A–E based on the sequence of the entire VP1 region. The predominant CVB3 strains in China belonged to cluster D, whereas cluster E CVB3 might be circulated globally compared to other clusters. The average nucleotide substitution rate in the P1 region of CVB3 was 4.82 × 10–3 substitutions/site/year. Myocarditis was more common with cluster A. Clusters C and D presented more cases of acute flaccid paralysis, and cluster D may be more likely to cause HFMD. Multiple recombination events were detected among CVB3 variants, and there were twenty-three recombinant lineages of CVB3 circulating worldwide.
Conclusions
Overall, this study provides full-length genomic sequences of CVB3 isolates with a wide geographic distribution over a long-term time scale in China, which will be helpful for understanding the evolution of this pathogen. Simultaneously, continuous surveillance of CVB3 is indispensable to determine its genetic diversity in China as well as worldwide.
“…To date, CVB3 strains are associated with various diseases, and the manifestations vary from mild respiratory [ 33 ], gastrointestinal infections [ 34 , 35 ], herpangina [ 36 ], and hand, foot, and mouth disease [ 7 , 8 , 37 ], to more severe diseases such as heart disease (including viral myocarditis [ 6 , 38 ], pericarditis [ 39 ], and acute myocardial infarction [ 40 ]), CNS involvement (meningitis [ 30 , 36 , 41 – 43 ], meningo-cerebellitis [ 11 ], encephalitis [ 44 ], and AFP [ 45 – 47 ]), and pancreatic interrelated disease (pancreatitis [ 48 ], diabetes [ 49 ]). More seriously, the virus can cause neonatal sepsis-like illness and sudden death in infected infants [ 38 , 50 ] and adults with low immune function.…”
Section: Resultsmentioning
confidence: 99%
“…Coxsackievirus B3 (CVB3) was first reported in Connecticut, the USA in 1949, and has emerged as an active pathogen in myocarditis [ 6 ], aseptic meningitis (AM), HFMD [ 7 , 8 ], and pancreatitis [ 9 ], causing a heavy burden on society. CVB3 infection is the most common cause of viral myocarditis, characterized by viral infection and myocardial inflammation [ 10 , 11 ].…”
Background
Coxsackievirus B3 (CVB3) has emerged as an active pathogen in myocarditis, aseptic meningitis, hand, foot, and mouth disease (HFMD), and pancreatitis, and is a heavy burden on public health. However, CVB3 has not been systematically analyzed with regard to whole-genome diversity and recombination. Therefore, this study was undertaken to systematically examine the genetic characteristics of CVB3 based on its whole genome.
Methods
We combined CVB3 isolates from our national HFMD surveillance and global sequences retrieved from GenBank. Phylogenetic analysis was performed to examine the whole genome variety and recombination forms of CVB3 in China and worldwide.
Results
Phylogenetic analysis showed that CVB3 strains isolated worldwide could be classified into clusters A–E based on the sequence of the entire VP1 region. The predominant CVB3 strains in China belonged to cluster D, whereas cluster E CVB3 might be circulated globally compared to other clusters. The average nucleotide substitution rate in the P1 region of CVB3 was 4.82 × 10–3 substitutions/site/year. Myocarditis was more common with cluster A. Clusters C and D presented more cases of acute flaccid paralysis, and cluster D may be more likely to cause HFMD. Multiple recombination events were detected among CVB3 variants, and there were twenty-three recombinant lineages of CVB3 circulating worldwide.
Conclusions
Overall, this study provides full-length genomic sequences of CVB3 isolates with a wide geographic distribution over a long-term time scale in China, which will be helpful for understanding the evolution of this pathogen. Simultaneously, continuous surveillance of CVB3 is indispensable to determine its genetic diversity in China as well as worldwide.
“…Multiple enteroviruses, including EV71 (types A, B, and C), CA16, and CVB3, are associated with HFMD diseases ( 30 ). We detected the antiviral spectrums of FOPMC and FIOMC by infecting RD cells with five virus strains.…”
“…3 Severe HFMD is often accompanied by neurological complications, including encephalitis, aseptic meningitis, pulmonary edema, and cardiorespiratory failure. 4 Toll-like receptors (TLRs) are an important class of protein molecules involved in nonspecific immunity that can recognize the conserved structure of biomolecules derived from microorganisms and induce antimicrobial immune responses. 5 After identifying the pathogens, TLRs can activate a variety of signaling pathways, including downstream MyD88-independent and MyD88-dependent pathways, which regulate the expression of a range of inflammatory cytokines and participate in inflammation and immune responses.…”
Section: Introductionmentioning
confidence: 99%
“…EV‐A71‐associated HFMD may lead to central nervous system damage and is associated with higher mortality and morbidity among infected patients, while CA16 infection is usually self‐limited with mild clinical symptoms 3 . Severe HFMD is often accompanied by neurological complications, including encephalitis, aseptic meningitis, pulmonary edema, and cardiorespiratory failure 4 …”
Hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) is a contagious viral disease, and toll-like receptors (TLRs) play essential roles in resisting the pathogen. The aim of this study was to assess the potential relationship between several TLRs polymorphisms and the HFMD severity in a Chinese children population. A total of 328 Chinese children with HFMD were included in the present study. The polymorphisms of TLR3 (
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