ABSTRACT
Echovirus 30 (E30), a member of the species B Enterovirus family, is a primary pathogen responsible for aseptic meningitis and encephalitis. E30 is associated with severe nervous system diseases and is a primary cause of child illness, disability, and even mortality. However, the mechanisms underlying E30-induced brain injury remain poorly understood. In this study, we used a neonatal mouse model of E30 to investigate the possible mechanisms of brain injury. E30 infection triggered the activation of microglia in the mouse brain and efficiently replicated within HMC3 cells. Subsequent transcriptomic analysis revealed inflammatory activation of microglia in response to E30 infection. We also detected a significant upregulation of polo-like kinase 1 (PLK1) and found that its inhibition could limit E30 infection in a sucking mouse model. Collectively, E30 infection led to brain injury in a neonatal mouse model, which may be related to excessive inflammatory responses. Our findings highlight the intricate interplay between E30 infection and neurological damage, providing crucial insights that could guide the development of interventions and strategies to address the severe clinical manifestations associated with this pathogen.
Subject(s)
Brain , Disease Models, Animal , Enterovirus B, Human , Microglia , Animals , Mice , Brain/virology , Brain/pathology , Enterovirus B, Human/pathogenicity , Enterovirus B, Human/physiology , Microglia/virology , Microglia/immunology , Cell Line , Humans , Inflammation/virology , Animals, Suckling , Animals, Newborn , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Echovirus Infections/virology , Virus ReplicationABSTRACT
After the first phase of the COVID-19 pandemic in Europe, a new highly pathogenic variant of echovirus 11 (E11) was detected. The aim of this study was to analyze the genetic diversity of Polish E11 environmental and clinical strains circulating between 2017 and 2023 as well as compare them with E11 strains isolated from severe neonatal sepsis cases reported in Europe between 2022 and 2023. Additionally, the study explores the effectiveness of environmental monitoring in tracking the spread of new variants. For this purpose, the complete sequences of the VP1 capsid protein gene were determined for 266 E11 strains isolated in Poland from 2017 to 2023, and phylogenetic analysis was performed. In the years 2017-2023, a significant increase in the detection of E11 strains was observed in both environmental and clinical samples in Poland. The Polish E11 strains represented three different genotypes, C3, D5 and E, and were characterized by a high diversity. In Poland, the intensive circulation of the new variant E11, responsible for severe neonatal infections with a high mortality in Europe, was detected in the years 2022-2023. This investigation demonstrates the important role of environmental surveillance in the tracking of enteroviruses circulation, especially in settings with limited clinical surveillance.
Subject(s)
COVID-19 , Enterovirus B, Human , Phylogeny , SARS-CoV-2 , Poland/epidemiology , Humans , Enterovirus B, Human/genetics , Enterovirus B, Human/classification , Enterovirus B, Human/isolation & purification , COVID-19/epidemiology , COVID-19/virology , SARS-CoV-2/genetics , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Genotype , Genetic Variation , Capsid Proteins/genetics , Infant, Newborn , Echovirus Infections/epidemiology , Echovirus Infections/virology , PandemicsABSTRACT
Echovirus 11 (E11) has gained attention owing to its association with severe neonatal infections. From 2018 to 2023, a surge in severe neonatal cases and fatalities linked to a novel variant of genotype D5 was documented in China, France, and Italy. However, the prevention and control of E11 variants have been hampered by limited background data on the virus circulation and genetic variance. Therefore, the present study investigated the circulating dynamics of E11 and the genetic variation and molecular evolution of genotype D5 through the collection of strains from the national acute flaccid paralysis (AFP) and hand, foot, and mouth disease (HFMD) surveillance system in China during 2000-2022 and genetic sequences published in the GenBank database. The results of this study revealed a prevalent dynamic of E11 circulation, with D5 being the predominant genotype worldwide. Further phylogenetic analysis of genotype D5 indicated that it could be subdivided into three important geographic clusters (D5-CHN1: 2014-2019, D5-CHN2: 2016-2022, and D5-EUR: 2022-2023). Additionally, variant-specific (144) amino acid mutation sites and positive-selection pressure sites (132, 262) were identified in the VP1 region. Cluster-specific recombination patterns were also identified, with CVB5, E6, and CVB4 as the major recombinant viruses. These findings provide a preliminary landscape of E11 circulation worldwide and basic scientific data for further study of the pathogenicity of E11 variants.
Subject(s)
Enterovirus B, Human , Evolution, Molecular , Genetic Variation , Genotype , Phylogeny , China/epidemiology , Humans , Enterovirus B, Human/genetics , Enterovirus B, Human/classification , Enterovirus B, Human/isolation & purification , Infant, Newborn , Echovirus Infections/virology , Echovirus Infections/epidemiology , Hand, Foot and Mouth Disease/virology , Hand, Foot and Mouth Disease/epidemiology , InfantABSTRACT
OBJECTIVES: A new variant of echovirus 11 (E11) infection is a major health concern in neonates. Here, we describe the clinical and virological characteristics of enterovirus (EV) infections in children hospitalized with acute respiratory infection in Southern Italy. METHODS: Between July 2022 and August 2023, 173 EV infections were identified. Demographic and clinical characteristics, comorbidities, and coinfections were analyzed. Genotypes were identified by sequencing of VP1. Whole-genome sequencing of five E11 strains was performed. RESULTS: Case numbers peaked in July 2022, November-December 2022, and June-July 2023. Coxsackievirus A2 was identified in 36.7%, coxsackievirus B5 in 13.8%, echovirus E11 in 9.2%, and EV-D68 in 6.4% of cases. No child had critical symptoms or a severe infection. The only neonate infected by E11 recovered fully after 5 days in hospital. Phylogenetic analysis revealed that four E11 strains were closely related to divergent lineage I E11 strains identified in France and Italy. CONCLUSIONS: The new variant of E11 was identified in children in Southern Italy. Although the cases were mild, the data suggest that transmission routes and host factors are likely to be main drivers for the development of potentially severe diseases. Systematic epidemiological/molecular surveillance will help us better understand the clinical impact of EV infections and develop preventive strategies.
Subject(s)
Enterovirus B, Human , Genotype , Phylogeny , Respiratory Tract Infections , Whole Genome Sequencing , Humans , Italy/epidemiology , Infant , Respiratory Tract Infections/virology , Respiratory Tract Infections/epidemiology , Male , Child, Preschool , Female , Enterovirus B, Human/genetics , Enterovirus B, Human/classification , Enterovirus B, Human/isolation & purification , Infant, Newborn , Child , Enterovirus Infections/epidemiology , Enterovirus Infections/virology , Hospitalization , Child, Hospitalized , Enterovirus/genetics , Enterovirus/classification , Enterovirus/isolation & purification , Echovirus Infections/epidemiology , Echovirus Infections/virology , Acute Disease , Coinfection/virology , Coinfection/epidemiologyABSTRACT
Echovirus 11 (E11) has gained attention owing to its association with severe neonatal infections. Due to the limited data available, the World Health Organization (WHO) considers public health risk to the general population to be low. The present study investigated the genetic variation and molecular evolution of E11 genomes collected from May to December 2023. Whole genome sequencing (WGS) was performed for 16 E11 strains. Phylogenetic analysis on WG showed how all Italian strains belonged to genogroup D5, similarly to other E11 strains recently reported in France and Germany all together aggregated into separate clusters. A cluster-specific recombination pattern was also identified using phylogenetic analysis of different genome regions. Echovirus 6 was identified as the major recombinant virus in 3Cpro and 3Dpol regions. The molecular clock analysis revealed that the recombination event probably occurred in June 2018 (95% HPD interval: Jan 2016-Jan 2020). Shannon entropy analyses, within P1 region, showed how 11 amino acids exhibited relatively high entropy. Five of them were exposed on the canyon region which is responsible for receptor binding with the neonatal Fc receptor. The present study showed the recombinant origin of a new lineage of E11 associated with severe neonatal infections.
Subject(s)
Echovirus Infections , Enterovirus B, Human , Genome, Viral , Genotype , Phylogeny , Recombination, Genetic , Humans , Infant, Newborn , Genome, Viral/genetics , Enterovirus B, Human/genetics , Enterovirus B, Human/classification , Enterovirus B, Human/isolation & purification , Echovirus Infections/virology , Echovirus Infections/epidemiology , Genetic Variation , Whole Genome Sequencing , Evolution, Molecular , Italy/epidemiologyABSTRACT
Echoviruses are among the most common worldwide causes of aseptic meningitis, which can cause long-term sequelae and death, particularly in neonates. However, the mechanisms by which these viruses induce meningeal inflammation are poorly understood, owing at least in part to the lack of in vivo models that recapitulate this aspect of echovirus pathogenesis. Here, we developed an in vivo neonatal mouse model that recapitulates key aspects of echovirus-induced meningitis. We show that expression of the human homologue of the primary echovirus receptor, the neonatal Fc receptor (FcRn), is not sufficient for infection of the brains of neonatal mice. However, ablation of type I, but not III, interferon (IFN) signaling in mice expressing human FcRn permitted high levels of echovirus replication in the brain, with corresponding clinical symptoms, including delayed motor skills and hind-limb weakness. Using this model, we defined the immunological response of the brain to echovirus infection and identified key cytokines, such as granulocyte colony-stimulating factor (G-CSF) and interleukin 6 (IL-6), that were induced by this infection. Lastly, we showed that echoviruses specifically replicate in the leptomeninges, where they induce profound inflammation and cell death. Together, this work establishes an in vivo model of aseptic meningitis associated with echovirus infections that delineates the differential roles of type I and type III IFNs in echovirus-associated neuronal disease and defines the specificity of echoviral infections within the meninges. IMPORTANCE Echoviruses are among the most common worldwide causes of aseptic meningitis, which can cause long-term sequelae or even death. The mechanisms by which echoviruses infect the brain are poorly understood, largely owing to the lack of robust in vivo models that recapitulate this aspect of echovirus pathogenesis. Here, we establish a neonatal mouse model of echovirus-induced aseptic meningitis and show that expression of the human homologue of the FcRn, the primary receptor for echoviruses, and ablation of type I IFN signaling are required to recapitulate echovirus-induced meningitis and clinical disease. These findings provide key insights into the host factors that control echovirus-induced meningitis and a model that could be used to test anti-echovirus therapeutics.
Subject(s)
Central Nervous System Infections , Echovirus Infections , Meningitis, Aseptic , Animals , Central Nervous System Infections/physiopathology , Central Nervous System Infections/virology , Echovirus Infections/complications , Echovirus Infections/physiopathology , Echovirus Infections/virology , Enterovirus B, Human/physiology , Humans , Inflammation , Interferon Type I/metabolism , Interferons , Meningitis, Aseptic/etiology , Meningitis, Aseptic/physiopathology , Meningitis, Aseptic/virology , Mice , Interferon LambdaABSTRACT
Echovirus 11 (E11) is a neurotropic virus that occasionally causes fatal neurological diseases in infected children. However, the molecular mechanism underlying the disease and pathological spectrum of E11 infection remains unclear. Therefore, we modelled E11 infection in 2-day-old type I interferon receptor knockout (IFNAR-/-) mice, which are susceptible to enteroviruses, with E11, and identified symptoms consistent with the clinical signs observed in human cases. All organs of infected suckling mice were found to show viral replication and pathological changes; the muscle tissue showed the highest viral replication, whereas the brain and muscle tissues showed the most obvious pathological changes. Brain tissues showed oedema and a large number of dead nerve cells; RNA-Seq analysis of the brain and hindlimb muscle tissues revealed differentially expressed genes to be abundantly enriched in immune response-related pathways, with changes in the Guanylate-binding protein (GBP) and MHC class genes, causing aseptic meningitis-related symptoms. Furthermore, human glioma U251 cell was identified as sensitive target cells for E11 infection. Overall, these results provide new insights into the pathogenesis and progress of aseptic meningitis caused by E11.
Subject(s)
Brain/pathology , Brain/virology , Echovirus Infections/pathology , Echovirus Infections/virology , Enterovirus B, Human/physiology , Animals , Animals, Newborn , Brain/metabolism , Cell Line, Tumor , Disease Models, Animal , Echovirus Infections/genetics , Humans , Meningitis, Aseptic/genetics , Meningitis, Aseptic/pathology , Meningitis, Aseptic/virology , Mice , Mice, Knockout , Muscle, Skeletal/pathology , Muscle, Skeletal/virology , RNA-Seq , Receptor, Interferon alpha-beta/genetics , Transcriptome , Viral Load , Virus ReplicationABSTRACT
Echovirus 6 (E6) is associated with various clinical diseases and is frequently detected in environmental sewage. Despite its high prevalence in humans and the environment, little is known about its molecular phylogeography in mainland China. In this study, 114 of 21,539 (0.53%) clinical specimens from hand, foot, and mouth disease (HFMD) cases collected between 2007 and 2018 were positive for E6. The complete VP1 sequences of 87 representative E6 strains, including 24 strains from this study, were used to investigate the evolutionary genetic characteristics and geographical spread of E6 strains. Phylogenetic analysis based on VP1 nucleotide sequence divergence showed that, globally, E6 strains can be grouped into six genotypes, designated A to F. Chinese E6 strains collected between 1988 and 2018 were found to belong to genotypes C, E, and F, with genotype F being predominant from 2007 to 2018. There was no significant difference in the geographical distribution of each genotype. The evolutionary rate of E6 was estimated to be 3.631 × 10-3 substitutions site-1 year-1 (95% highest posterior density [HPD]: 3.2406 × 10-3-4.031 × 10-3 substitutions site-1 year-1) by Bayesian MCMC analysis. The most recent common ancestor of the E6 genotypes was traced back to 1863, whereas their common ancestor in China was traced back to around 1962. A small genetic shift was detected in the Chinese E6 population size in 2009 according to Bayesian skyline analysis, which indicated that there might have been an epidemic around that year.
Subject(s)
Echovirus 6, Human/genetics , Echovirus Infections/epidemiology , Echovirus Infections/virology , Capsid Proteins/genetics , China/epidemiology , Echovirus 6, Human/classification , Echovirus 6, Human/isolation & purification , Evolution, Molecular , Genotype , Hand, Foot and Mouth Disease/epidemiology , Hand, Foot and Mouth Disease/virology , Humans , Molecular Epidemiology , Phylogeny , Prevalence , RNA, Viral/geneticsABSTRACT
Echovirus 30 (E30), a member of the enterovirus B species, is a major cause of viral meningitis, targeting children and adults alike. While it is a frequently isolated enterovirus and the cause of several outbreaks all over the world, surprisingly little is known regarding its entry and replication strategy within cells. In this study, we used E30 strain Bastianni (E30B) generated from an infectious cDNA clone in order to study early entry events during infection in human RD cells. E30B required the newly discovered Fc echovirus receptor (FcRn) for successful infection, but not the coxsackievirus and adenovirus receptor (CAR) or decay-accelerating factor (DAF), although an interaction with DAF was observed. Double-stranded RNA replication intermediate was generated between 2 and 3 h postinfection (p.i.), and viral capsid production was initiated between 4 and 5 h p.i. The drugs affecting Rac1 (NSC 23766) and cholesterol (filipin III) compromised infection, whereas bafilomycin A1, dyngo, U-73122, wortmannin, and nocodazole did not, suggesting the virus follows an enterovirus-triggered macropinocytic pathway rather than the clathrin pathway. Colocalization with early endosomes and increased infection due to constitutively active Rab5 expression suggests some overlap and entry to classical early endosomes. Taken together, these results suggest that E30B induces an enterovirus entry pathway, leading to uncoating in early endosomes.IMPORTANCE Echovirus 30 (E30) is a prevalent enterovirus causing regular outbreaks in both children and adults in different parts of the world. It is therefore surprising that relatively little is known of its infectious entry pathway. We set out to generate a cDNA clone and gradient purified the virus in order to study the early entry events in human cells. We have recently studied other enterovirus B group viruses, like echovirus 1 (EV1) and coxsackievirus A9 (CVA9), and found many similarities between those viruses, allowing us to define a so-called "enterovirus entry pathway." Here, E30 is reminiscent of these viruses, for example, by not relying on acidification for infectious entry. However, despite not using the clathrin entry pathway, E30 accumulates in classical early endosomes.
Subject(s)
Echovirus Infections/physiopathology , Enterovirus B, Human/genetics , Enterovirus B, Human/metabolism , A549 Cells , Animals , CHO Cells , Cell Line , Cricetulus , Disease Outbreaks , Echovirus Infections/virology , Enterovirus/genetics , Enterovirus B, Human/pathogenicity , Enterovirus Infections/virology , Humans , Phylogeny , RNA, Viral/genetics , Receptors, Fc/genetics , Sequence Analysis, DNA/methods , Virus Internalization , Virus ReplicationABSTRACT
A regional epidemic of aseptic meningitis caused by echovirus 30 (E30) occurred in Hokkaido, Japan, during the period of August-December 2017. To investigate their phylogenetic relationship to other human enteroviruses, we determined the complete genomic nucleotide sequences of isolates from this outbreak. Phylogenetic analysis of the viral capsid protein 1 gene showed that the strains were most closely related to E30 strains detected in Germany, France, and Russia in 2013. In contrast, the region encoding the viral protease and the RNA-dependent RNA polymerase had a close phylogenetic relationship to non-E30 enteroviruses detected in the United Kingdom and Switzerland in 2015-2017, suggesting that a recombination event had occurred.
Subject(s)
Echovirus Infections/virology , Enterovirus B, Human/genetics , Meningitis, Aseptic/virology , Capsid Proteins/genetics , Disease Outbreaks , Enterovirus Infections/virology , Epidemics , France , Genotype , Germany , Humans , Japan , Molecular Epidemiology/methods , Phylogeny , RNA, Viral/genetics , Russia , Sequence Analysis, DNA/methods , Switzerland , United KingdomABSTRACT
Echovirus 11 (E-11) is one of the most frequently isolated enteroviruses causing meningitis and other diseases such as hand, foot, and mouth disease (HFMD) and acute flaccid paralysis (AFP). Fifty-nine newly determined E-11 VP1 sequences from the China AFP and HFMD surveillance network and 500 E-11 VP1 sequences obtained from the GenBank database, which were associated with 12 categories of diseases, were screened for phylogenetic analysis. Based on the standard method of genotype classification, E-11 strains circulated worldwide were reclassified into six genotypes as A, B, C, D, E, and F, in which genotype F is newly divided, and genotypes A and C are further divided into A1-5 and C1-4 by this research, whereas genotype D was still divided into D1-5 as in a previous study of Oberste et al. Sub-genotype A1 was the predominant sub-genotype in mainland China between 2008-2017, whereas sub-genotype D5 was the predominant sub-genotype circulated outside China from 1998-2014. However, genotype and sub-genotype spectra showed statistical significance among AFP and HFMD cases (χ2 = 60.86, P < 0.001), suggesting that different genotypes might have a tendency to cause different diseases. Strengthening the surveillance of E-11 might provide further information about pathogenic evolution or specific nucleotide mutation associated with different clinical diseases.
Subject(s)
Echovirus Infections/epidemiology , Enterovirus B, Human/genetics , China/epidemiology , Echovirus Infections/virology , Enterovirus B, Human/classification , Genotype , Humans , PhylogenyABSTRACT
BACKGROUND: Echovirus 30 (E30) is one of the most common causative agents for aseptic meningitis. OBJECTIVES: In the autumn of 2017, there was an outbreak caused by E30 in Kushiro, Hokkaido, Japan. The aim of this study was to characterize this outbreak. STUDY DESIGN: Fifty-nine patients were admitted to the Department of Pediatrics, Kushiro Red Cross Hospital (KRCH) with clinical diagnosis of aseptic meningitis. Among those, 36 patients were finally diagnosed as E30-associated aseptic meningitis by the detection of viral RNA using reverse transcription-polymerase chain reaction (RT-PCR) and/or the evidence of more than four-fold rise in neutralizing antibody (NA) titers in the convalescent phase relative to those in the acute phase. We investigated these 36 confirmed cases. RESULTS: The median age was 6 years (range: 6 months-14 years). The positive signs and symptoms were as follows: fever (100%), headache (94%), vomiting (92%), jolt accentuation (77%), neck stiffness (74%), Kernig sign (29%), and abdominal pain (28%). The median cerebrospinal fluid (CSF) white cell count, neutrophil count, and lymphocyte count were 222/µL (range: 3-1434/µL), 144/µL (range: 1-1269/µL), and 85/µL (range: 2-354/µL), respectively. Although the detected viral genes demonstrated same cluster, they were different from E30 strains observed in Japan between 2010 and 2014. CONCLUSION: We mainly showed clinical and virological features of the E30-associated aseptic meningitis outbreak that occurred in Kushiro. To prevent further spread of E30 infection, continuous surveillance of enterovirus (EV) circulation and standard precautions are considered essential.
Subject(s)
Disease Outbreaks , Echovirus Infections/epidemiology , Echovirus Infections/virology , Enterovirus B, Human/isolation & purification , Meningitis, Aseptic/epidemiology , Meningitis, Aseptic/virology , Adolescent , Antibodies, Neutralizing/blood , Cerebrospinal Fluid/cytology , Child , Child, Preschool , Echovirus Infections/pathology , Echovirus Infections/physiopathology , Enterovirus B, Human/classification , Enterovirus B, Human/genetics , Enterovirus B, Human/immunology , Female , Genotype , Hospitals, Pediatric , Humans , Infant , Japan/epidemiology , Male , Meningitis, Aseptic/pathology , Meningitis, Aseptic/physiopathology , Phylogeny , RNA, Viral/genetics , Viral Proteins/geneticsSubject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Echovirus Infections/virology , Immunocompromised Host , Immunologic Factors/adverse effects , Massive Hepatic Necrosis/virology , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Adult , Basiliximab/therapeutic use , Echovirus Infections/immunology , Female , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/therapeutic use , Liver Transplantation , Massive Hepatic Necrosis/immunology , Massive Hepatic Necrosis/surgery , Tacrolimus/therapeutic useABSTRACT
Echoviruses are amongst the most common causative agents of aseptic meningitis worldwide and are particularly devastating in the neonatal population, where they are associated with severe hepatitis, neurological disease, including meningitis and encephalitis, and even death. Here, we identify the neonatal Fc receptor (FcRn) as a pan-echovirus receptor. We show that loss of expression of FcRn or its binding partner beta 2 microglobulin (ß2M) renders cells resistant to infection by a panel of echoviruses at the stage of virus attachment, and that a blocking antibody to ß2M inhibits echovirus infection in cell lines and in primary human intestinal epithelial cells. We also show that expression of human, but not mouse, FcRn renders nonpermissive human and mouse cells sensitive to echovirus infection and that the extracellular domain of human FcRn directly binds echovirus particles and neutralizes infection. Lastly, we show that neonatal mice expressing human FcRn are more susceptible to echovirus infection by the enteral route. Our findings thus identify FcRn as a pan-echovirus receptor, which may explain the enhanced susceptibility of neonates to echovirus infections.
Subject(s)
Enterovirus B, Human/genetics , Histocompatibility Antigens Class I/genetics , Receptors, Fc/genetics , Receptors, Virus/genetics , beta 2-Microglobulin/genetics , Animals , Echovirus Infections/genetics , Echovirus Infections/immunology , Echovirus Infections/virology , Enterovirus B, Human/pathogenicity , Humans , Immunoglobulin G/genetics , Immunoglobulin G/immunology , Intestinal Mucosa/cytology , Intestinal Mucosa/metabolism , Mice , Protein Binding , beta 2-Microglobulin/immunologyABSTRACT
OBJECTIVES: To describe an outbreak of acute myalgia accompanied by elevated levels of muscle enzymes that occurred in the northeast region of Brazil from December 2016 through to May 2017. METHODS: Clinical data were analysed and laboratory tests were performed in 86 specimens obtained from 52 individuals with suspected acute myalgia. A broader reactive enterovirus real-time RT-PCR followed by a semi-nested PCR amplification of partial VP1 gene were performed to identify the causative agent. RESULTS: Eighty-six clinical samples were received in our laboratory during the myalgia outbreak. Median age of individuals was 39 years. Sudden acute myalgia and dark urine were the most common symptoms. Creatine phosphokinase levels were elevated with mean value â¼16 893 U/L. Human enterovirus was detected in 67% (58/86) of the patient's specimens (urine, serum, faeces and rectal swab). The enterovirus positivity per patient was 82.7% (43/52). Echovirus 30 (E-30) (82% of the typed specimens, 18/22; 76.4% (13/17) of the typed specimens per patient) was the main enterovirus identified. In addition to E-30, CV-A16 (1/22) and E-6 (3/22) were detected in 4% and 14% of the typed specimens, respectively. No deaths occurred. CONCLUSION: The 2016-2017 outbreak of acute myalgia that occurred in the northeast region of Brazil can be associated with E-30. Despite the clinical manifestations, a favourable outcome was observed for all patients.
Subject(s)
Echovirus Infections/virology , Enterovirus B, Human/isolation & purification , Myalgia/virology , Rhabdomyolysis/virology , Adolescent , Adult , Aged , Brazil/epidemiology , Child , Echovirus Infections/epidemiology , Echovirus Infections/pathology , Female , Humans , Male , Middle Aged , Myalgia/epidemiology , Rhabdomyolysis/epidemiology , Young AdultABSTRACT
An upsurge in Echovirus 30 (E30) infections, associated with meningitis/meningoencephalitis, has been observed in Denmark, Germany, the Netherlands, Norway and Sweden in the period April to September 2018, compared with 2015-2017. In total, 658 E30 infections among 4,537 enterovirus infections were detected in 15 countries between January and September 2018 and affected mainly newborns and 26-45 year-olds. National public health institutes are reminded to remain vigilant and inform clinicians of the ongoing epidemic.
Subject(s)
Disease Outbreaks , Echovirus Infections/epidemiology , Enterovirus B, Human/isolation & purification , Meningitis, Aseptic/epidemiology , Adolescent , Adult , Aged , Child , Child, Preschool , Denmark/epidemiology , Echovirus Infections/cerebrospinal fluid , Echovirus Infections/diagnosis , Echovirus Infections/virology , Enterovirus B, Human/genetics , Genotype , Germany/epidemiology , Humans , Infant , Meningitis, Aseptic/diagnosis , Meningitis, Aseptic/virology , Middle Aged , Netherlands/epidemiology , Norway/epidemiology , Phylogeny , RNA, Viral , Sequence Analysis, DNA , Sweden/epidemiology , Young AdultABSTRACT
Background: Acute respiratory infection result in high mortality and morbidity worldwide. There are several viral factors that originate respiratory diseases among them Enteroviruses(EVs) and Human Rhinoviruses(HRVs) can be mentioned. HRVs and EVs belong to Picornaviridae family and they have been recently classified under Enteroviruses. The pattern of respiratory infections generating organisms varies according to geographical locations. Therefore, it seems necessary to organize an appropriate plan to manage common viral diseases exclusively about Rhinoviruses and Enteroviruses. PATIENT AND METHODS: A total of 100 samples were collected from patients with acute respiratory infections (ARIs) who were hospitalized in Ahvaz city hospitals during December 2012 to November 2013 (one year longitude). Semi-Nested PCR was done on samples for detection of HRVs and EVs using region gene of VP4/VP2. Phylogenetic and molecular evolutionary analyses performed with MEGA version 5 software find out the sequence homology among the detected HRV and EV serotype. RESULTS: The results of this study revealed that from of 100 cases of ARIs 19 patients (19%) were HRV positive and 3 (3%) patients positive for EVs. Most positive cases of HRVs were observed in the autumn season while 3 positive cases of EVs were equally found in spring, summer and autumn. Phylogenetic analyses showed that the HRV strains were HRV-A9, HRV-A49, HRV-B14 and EV strains were Echo3 and 9. CONCLUSION: The results of this study revealed that high prevalence of 19% HRVs, HRV-A9, HRV-A49, HRV-B14 serotypes and low frequency of 3% Echo Viruses, Echo3 and Echo 9 serotypes have been detected in patients with ARI.
Subject(s)
Enterovirus B, Human , Picornaviridae Infections , Respiratory Tract Infections , Rhinovirus , Echovirus Infections/epidemiology , Echovirus Infections/pathology , Echovirus Infections/virology , Enterovirus B, Human/classification , Enterovirus B, Human/genetics , Enterovirus B, Human/physiology , Humans , Phylogeny , Picornaviridae Infections/epidemiology , Picornaviridae Infections/pathology , Picornaviridae Infections/virology , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Rhinovirus/classification , Rhinovirus/genetics , Rhinovirus/physiology , Seasons , SerogroupSubject(s)
Echovirus Infections/virology , Enterovirus B, Human/isolation & purification , Hand, Foot and Mouth Disease/virology , Immunocompetence , DNA, Viral/genetics , Echovirus Infections/diagnosis , Echovirus Infections/immunology , Enterovirus B, Human/genetics , Enterovirus B, Human/immunology , Enterovirus B, Human/pathogenicity , Female , Hand, Foot and Mouth Disease/diagnosis , Hand, Foot and Mouth Disease/immunology , Humans , Middle Aged , Remission, SpontaneousABSTRACT
Recombination has been recognized as a major mechanism of evolution in enteroviruses. The Echovirus 30 (E-30) strain Gior was sequenced and phylogenetically compared to all available E-30 sequences to detect recombination events between the 5ÎUTR and VP1 genomic regions. The comparison of phylogenetic trees of the 5ÎUTR and VP1 revealed incongruences concerning strains, lineages and sub-lineages. Comparative analysis of 62 E-30 sub-genomic sequences revealed six different recombination events that almost all occurred in the same region, having a start point in the 3Îend of the 5Î UTR and end point in VP4. The only exception was the sub-lineage of Gior for which both borders of recombination were located in the 5ÎUTR. These results describe for the first time recombination events in this region in circulating EV-B strains, revealing the exact points of these recombination events, highlighting the impact of such events on the evolution and epidemiology of enteroviruses.
Subject(s)
Echovirus Infections/virology , Enterovirus B, Human/genetics , Recombination, Genetic , Viral Proteins/genetics , 5' Untranslated Regions , Enterovirus B, Human/classification , Enterovirus B, Human/isolation & purification , Enterovirus B, Human/physiology , Evolution, Molecular , Genome, Viral , Humans , Phylogeny , RNA, Viral/genetics , Serogroup , Viral Proteins/metabolismABSTRACT
BACKGROUND: Echovirus 6 (E6) infections are associated with aseptic meningitis and acute flaccid paralysis (AFP). But some infections, sometimes most of them, are asymptomatic. The mechanism of E6 virulence is unknown. Analyses of the molecular evolution of asymptomatic E6 may help understand why the infections show different manifestations. METHODS: Ninety-six stool samples of healthy children in Yunnan, China were collected and two E6 strains were isolated from them. The whole genomes of these two E6 strains were sequenced, and their molecular evolution was analyzed. RESULTS: The results showed that the two E6 strains may be derived from KJ7724XX strains, which were predominant in AFP patients in Shangdong in 2011. The evolution was accelerated when the two E6 strains formed, although no positive selection site was found. The 11 exclusive mutations on which selection force significantly changed were found in the 2C, 3AB and 3C genes. CONCLUSION: There are some E6 strains which did not cause the disease in the children of Yunnan. These E6 strains maybe come from a recombinant E6 strain which was associated with the outbreak of AFP in Shangdong in 2011. However, some new mutations were found in the 2C, 3AB and 3C genes of these asymptomatic strains, and these mutations may be constraint by the natural selection and could be potentially responsible for clinical presentations.