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1.
J Clin Virol ; 173: 105691, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38749308

RESUMEN

BACKGROUND: The increasing incidence of hand, foot, and mouth disease (HFMD) associated with Coxsackievirus A6 (CVA6) has become a very significant public health problem. The aim of this study is to investigate the recombination, geographic transmission, and evolutionary characteristics of the global CVA6. METHODS: From 2019 to 2022, 73 full-length CVA6 sequences were obtained from HFMD patients in China and analyzed in combination with 1032 published whole genome sequences. Based on this dataset, the phylogenetic features, recombinant diversity, Bayesian phylodynamic characteristics, and key amino acid variations in CVA6 were analyzed. RESULTS: The four genotypes of CVA6, A, D, E, and F, are divided into 24 recombinant forms (RFs, RF-A - RF-X) based on differences in the P3 coding region. The eastern China region plays a key role in the dissemination of CVA6 in China. VP1-137 and VP1-138 are located in the DE loop on the surface of the CVA6 VP1 protein, with the former being a highly variable site and the latter having more non-synonymous substitutions. CONCLUSIONS: Based on whole genome sequences, this study contributes to the CVA6 monitoring, early warning, and the pathogenic mechanism by studying recombination diversity, geographical transmission characteristics, and the variation of important amino acid sites.


Asunto(s)
Evolución Molecular , Genotipo , Enfermedad de Boca, Mano y Pie , Filogenia , Recombinación Genética , Humanos , China/epidemiología , Enfermedad de Boca, Mano y Pie/virología , Enfermedad de Boca, Mano y Pie/epidemiología , Genoma Viral , Secuenciación Completa del Genoma , Enterovirus/genética , Enterovirus/clasificación , Enterovirus/aislamiento & purificación , Variación Genética , Teorema de Bayes
2.
Sci Rep ; 9(1): 13668, 2019 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-31541120

RESUMEN

Sporadic outbreaks caused by coxsackievirus A4 (CV-A4) have been reported worldwide. To further elucidate the detailed genetic characteristics and evolutionary recombination events of CV-A4, virus samples from nationwide hand, foot and mouth disease (HFMD) surveillance, encompassing 27 out of the 31 provinces in China, were investigated. Comprehensive and systematic phylogenetic analyses were performed by using 29 complete genomes, 142 complete CV-A4 VP1 sequences. Four genotypes (A, B, C and D) and five sub-genotypes (C1-C5) were re-identified based on the complete VP1 sequences. C2 is the predominant sub-genotype of CV-A4 associated with HFMD and has evolved into 3 clusters. Cluster 1 is a major cluster that has been persistently and extensively circulating in China since 2006 and has been associated with all severe cases. All the sequences showed high homology with the CV-A4 prototype in the P1 region, while higher identities with CV-A5, CV-14 and CV-16 in the P2 and P3 regions. Recombination analysis revealed that C2 had two specific genetic recombination patterns with other EV-A prototypes in the 5'-UTR and 3D region compared with C5. These recombination patterns might be associated with the increased transmissibility of C2 viruses, which were obtained due to their persistent and extensive circulation in populations.


Asunto(s)
Proteínas de la Cápside/genética , Enterovirus Humano A/clasificación , Enterovirus Humano A/genética , Enfermedad de Boca, Mano y Pie/virología , Análisis de Secuencia de ARN/métodos , Línea Celular , China , Evolución Molecular , Genoma Viral , Genotipo , Humanos , Filogenia , Vigilancia de la Población , Recombinación Genética , Homología de Secuencia de Ácido Nucleico
3.
Arch Virol ; 160(4): 1097-104, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25680566

RESUMEN

Since 2008, Mainland China has undergone widespread outbreaks of hand, foot, and mouth disease (HFMD). In order to determine the characteristics of epidemics and enteroviruses (EV) associated with HFMD in Tianjin, in northern China, epidemiological and virological data from routine surveillance were collected and analyzed. In Tianjin, a persistent epidemic of HFMD was demonstrated during 2008-2013, involving 102,705 mild, 179 severe, and 16 fatal cases. Overall, 8234 specimens were collected from 7829 HFMD patients for EV detection during 2008-2013. Enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) were the dominant serotypes during 2008-2012, and they were replaced by CV-A6 as the major causative agent in 2013. Phylogenetic analysis based on complete VP1 nucleotide sequences revealed that multiple CV-A6 lineages co-circulated in Tianjin, which grouped together with strains from China and other countries and split into two distinct clusters (clusters 1 and 2). Most Tianjin strains grouped in cluster 1 and were closely related to strains from several eastern and southern provinces of China during 2012 and 2013. Estimates from Bayesian MCMC analysis suggested that multiple lineages had been transmitted silently before the outbreaks at an estimated evolutionary rate of 4.10 × 10(-3) substitutions per site per year without a specific distribution of rate variances among lineages. The sudden outbreak of CV-A6 in Tianjin during 2013 is attributed to indigenous CV-A6 lineages, which were linked to the wide spread of endemic strains around eastern and southern China.


Asunto(s)
Enterovirus Humano A/genética , Enfermedad de Boca, Mano y Pie/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , China/epidemiología , Brotes de Enfermedades , Enterovirus Humano A/clasificación , Enterovirus Humano A/aislamiento & purificación , Evolución Molecular , Femenino , Enfermedad de Boca, Mano y Pie/epidemiología , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Filogenia , Adulto Joven
4.
Microbiol Res ; 171: 39-44, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25644951

RESUMEN

The objective of this study was to determine the function of the novel uropathogenic Escherichia coli (UPEC) gene R049 during host infection. We infected the urinary tracts of mice with E. coli UPEC132 or the R049 deletion mutant UPEC132ΔR049.The mouse kidneys were harvested at 4 and 8h post-infection and screened for differentially expressed genes by microarray analysis. We identified 379 and 515 differentially expressed genes at 4 and 8 h post-infection, respectively. Thirty-four of these genes were associated with inflammatory and immune signaling pathways, including those related to mitogen-activated protein kinase signaling, leukocyte transendothelial migration, cytokine-cytokine receptor interaction, Toll-like receptor signaling, and apoptosis. Protein binding (GO 0005515) was the most prevalent molecular function in the Gene Ontology terms related to differentially expressed genes. In conclusion, R049 expression in UPEC132 is related to the early innate immune and inflammatory responses in UPEC-infected hosts. This work lays the foundation for further research on anti-infective immunity against UPEC.


Asunto(s)
Infecciones por Escherichia coli/microbiología , Proteínas de Escherichia coli/genética , Infecciones Urinarias/microbiología , Escherichia coli Uropatógena/genética , Animales , Carga Bacteriana , Biología Computacional , Modelos Animales de Enfermedad , Infecciones por Escherichia coli/genética , Infecciones por Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Femenino , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Riñón/metabolismo , Riñón/microbiología , Ratones , Anotación de Secuencia Molecular , Reproducibilidad de los Resultados , Transducción de Señal , Transcriptoma , Infecciones Urinarias/genética , Infecciones Urinarias/metabolismo , Escherichia coli Uropatógena/metabolismo
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