Genetic characterization of VP1 of coxsackieviruses A2, A4, and A10 associated with hand, foot, and mouth disease in Vietnam in 2012–2017: endemic circulation and emergence of new HFMD-causing lineages

Hoa-Tran, Thi Nguyen; Dao, Anh; Kataoka, Chikako; Ta, Hong Thi Thu; Nguyen, H.; Takemura, Taichiro; Nguyen, Thi-Hoai-Thu; Vu, Hung Manh; Nguyen, Thu Trang; Shimizu, Hiroyuki

doi:10.1007/s00705-020-04536-3

Cited by 17 publications

(11 citation statements)

References 51 publications

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“…According to previous studies, E6 and E11 have been the most commonly detected EV types, especially among patients showing severe central nervous system syndromes [16,30,33,[42][43][44]. In this investigation, EV-A71 was the main pathogen associated with AFP (7.6%), followed by E6 (7.3%) and E11 (6.7%) suggesting a high occurrence of these types from 2005 to 2017.…”

Section: Discussionsupporting

confidence: 49%

“…Thus, we explored the deduced amino acid sequences from the BC loop and surrounding regions of prototype strains and some viral types. Because length differences in VP1 were described in the amino terminal domain, the BC loop and carboxyl-terminal domain [28], we defined the VP1 BC-loop positions, as previously reported [29][30]. Among CVA2 isolates, the substitution A102S was found in almost all analyzed sequences.…”

Section: Amino Acid Substitutions In the Bc Loopmentioning

confidence: 99%

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Molecular characterization and epidemiological aspects of non-polio enteroviruses isolated from acute flaccid paralysis in Brazil: a historical series (2005–2017)

Sousa

Oliveira

Burlandy

et al. 2020

Emerging Microbes & Infections

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Due to the advanced stage of polio eradication, the possible role of non-polio enteroviruses (NPEVs) associated to acute flaccid paralysis (AFP) cases has been highlighted. In this study, we described epidemiological aspects of NPEVs infections associated to AFP and explore the viral genetic diversity, information still scarce in Brazil. From 2005 to 2017, 6707 stool samples were collected in the scope of the Brazilian Poliomyelitis Surveillance Program. NPEVs were isolated in 359 samples (5.3%) and 341 (94.9%) were genotyped. About 46 different NPEV types were identified with the following detection pattern EV-B > EV-A > EV-C. The major EV-types were CVA2, CV4, EV-A71, CVB3, CVB5, E6, E7, E11, CVA13 and EV-C99, which corresponds to 51.6% of the total. Uncommon types, such as CVA12, EV-90 and CVA11, were also identified. Different E6 genogroups were observed, prevailing the GenIII, despite periods of co-circulation, and replacement of genogroups along time. CVA2 sequences were classified as genotype C and data suggested its dispersion in South-American countries. CVA13 viruses belonged to cluster B and Venezuelan viruses composed a new putative cluster. This study provides extensive information on enterovirus diversity associated with AFP, reinforcing the need of tailoring current surveillance strategies to timely monitor emergence/re-emergence of NPEVs.

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Section: Discussionsupporting

confidence: 49%

Section: Amino Acid Substitutions In the Bc Loopmentioning

confidence: 99%

Molecular characterization and epidemiological aspects of non-polio enteroviruses isolated from acute flaccid paralysis in Brazil: a historical series (2005–2017)

Sousa

Oliveira

Burlandy

et al. 2020

Emerging Microbes & Infections

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“…Enterovirus (EV) 71 and several coxsackievirus (CV) serotypes (CVA2, A4, and A10) are frequently implicated in hand-foot-mouth disease (HFMD). Among the pathogens of HFMD, CVA2 has emerged as an active pathogen that has been implicated in HFMD and herpangina outbreaks worldwide such as China [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ], Thailand [ 8 ], France [ 9 ], Vietnam [ 10 ] Brazil [ 11 ], and Korea [ 12 , 13 ], representing great socio-economic burden for the patient and society.…”

Section: Introductionmentioning

confidence: 99%

Coxsackievirus A2 Leads to Heart Injury in a Neonatal Mouse Model

Zhu

Liang

et al. 2021

Viruses

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Coxsackievirus A2 (CVA2) has emerged as an active pathogen that has been implicated in hand, foot, and mouth disease (HFMD) and herpangina outbreaks worldwide. It has been reported that severe cases with CVA2 infection develop into heart injury, which may be one of the causes of death. However, the mechanisms of CVA2-induced heart injury have not been well understood. In this study, we used a neonatal mouse model of CVA2 to investigate the possible mechanisms of heart injury. We detected CVA2 replication and apoptosis in heart tissues from infected mice. The activity of total aspartate transaminase (AST) and lactate dehydrogenase (LDH) was notably increased in heart tissues from infected mice. CVA2 infection also led to the disruption of cell-matrix interactions in heart tissues, including the increases of matrix metalloproteinase (MMP)3, MMP8, MMP9, connective tissue growth factor (CTGF) and tissue inhibitors of metalloproteinases (TIMP)4. Infiltrating leukocytes (CD45+ and CD11b+ cells) were observed in heart tissues of infected mice. Correspondingly, the expression levels of inflammatory cytokines in tissue lysates of hearts, including tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), IL6 and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in CVA2 infected mice. Inflammatory signal pathways in heart tissues, including phosphatidylinositol 3-kinase (PI3K)-AKT, mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB), were also activated after infection. In summary, CVA2 infection leads to heart injury in a neonatal mouse model, which might be related to viral replication, increased expression levels of MMP-related enzymes and excessive inflammatory responses.

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“…The relatively accepted method is based on the VP1 whole sequence; a difference of more than 15% in the primary sequence of VP1 is regarded as a different genotype, which includes A-D genotypes 26 , 27 with the addition of E-I genotypes later. 21 , 28–30 …”

Section: Discussionmentioning

confidence: 99%

Evaluation of the cross-neutralization activities elicited by Coxsackievirus A10 vaccine strains

Huo

Yang

Liu

et al. 2021

Human Vaccines & Immunotherapeutics

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Increased severity of diseases caused by Coxsackievirus A10 (CV-A10) as well as a large number of mutants and recombinants circulating in the population are a cause of concern for public health. A vaccine with broad-spectrum and homogenous protective capacity is needed to prevent outbreaks of CV-A10. Here, we evaluated cross-neutralization of prototype strain and 17 CV-A10 strains from related manufacturers in mainland China in vitro using 30 samples of plasma collected from naturally infected human adults and 18 sera samples from murine immunized with the above strains of CV-A10. Both human plasma and murine sera exhibited varying degrees of cross-neutralizing activities. Prototype A/Kowalik and sub-genotype C3/S113 were most difficult to neutralize. Among all strains tested, neutralization of S102 and S108 strains by 18 different sera was the most uniform, suggesting their suitability for detection of NtAb titers of different vaccines for avoiding biases introduced by detection strain. Furthermore, among all immune-sera, cross-neutralization of the 18 strains of CV-A10 by anti-S110 and anti-S102 was the most homogenous. Anti-S102 exhibiting higher geometric mean titer (GMT) in vitro was evaluated for its cross-protection capacity in vivo . Remarkably, administration of anti-S102 protected mice from lethal dosage of eight strains of CV-A10. These results provide a framework for formulating strategies for the R&D of vaccines targeting CV-A10 infections.

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Genetic characterization of VP1 of coxsackieviruses A2, A4, and A10 associated with hand, foot, and mouth disease in Vietnam in 2012–2017: endemic circulation and emergence of new HFMD-causing lineages

Cited by 17 publications

References 51 publications

Molecular characterization and epidemiological aspects of non-polio enteroviruses isolated from acute flaccid paralysis in Brazil: a historical series (2005–2017)

Molecular characterization and epidemiological aspects of non-polio enteroviruses isolated from acute flaccid paralysis in Brazil: a historical series (2005–2017)

Coxsackievirus A2 Leads to Heart Injury in a Neonatal Mouse Model

Evaluation of the cross-neutralization activities elicited by Coxsackievirus A10 vaccine strains

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