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1.
Viruses ; 13(12)2021 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-34960747

RESUMO

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.


Assuntos
Encéfalo/patologia , Encéfalo/virologia , Infecções por Echovirus/patologia , Infecções por Echovirus/virologia , Enterovirus Humano B/fisiologia , Animais , Animais Recém-Nascidos , Encéfalo/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Infecções por Echovirus/genética , Humanos , Meningite Asséptica/genética , Meningite Asséptica/patologia , Meningite Asséptica/virologia , Camundongos , Camundongos Knockout , Músculo Esquelético/patologia , Músculo Esquelético/virologia , RNA-Seq , Receptor de Interferon alfa e beta/genética , Transcriptoma , Carga Viral , Replicação Viral
2.
Proc Natl Acad Sci U S A ; 116(9): 3758-3763, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808762

RESUMO

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.


Assuntos
Enterovirus Humano B/genética , Antígenos de Histocompatibilidade Classe I/genética , Receptores Fc/genética , Receptores Virais/genética , Microglobulina beta-2/genética , Animais , Infecções por Echovirus/genética , Infecções por Echovirus/imunologia , Infecções por Echovirus/virologia , Enterovirus Humano B/patogenicidade , Humanos , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Camundongos , Ligação Proteica , Microglobulina beta-2/imunologia
3.
PLoS One ; 7(5): e36656, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22586486

RESUMO

BACKGROUND: Echovirus 30 (Echo30) is one of the most frequently identified human enteroviruses (EVs) causing aseptic meningitis and encephalitis. However the mechanism underlying the pathogenesis of Echo30 infection with significant clinical outcomes is not completely understood. The aim of this investigation is to illustrate molecular pathologic alteration in neuronal cells induced by Echo30 infection using clinical isolate from young patient with neurologic involvement. METHODOLOGY/PRINCIPAL FINDINGS: To characterize the neuronal cellular response to Echo30 infection, we performed a proteomic analysis based on two-dimensional gel electrophoresis (2-DE) and MALDI-TOF/TOF Mass Spectrophotometric (MS) analysis. We identified significant alteration of several protein expression levels in Echo30-infected SK-N-SH cells. Among these proteins, we focused on an outstanding up-regulation of Triple functional domain (TRIO) in Echo30-infected SK-N-SH cells. Generally, TRIO acts as a key component in the regulation of axon guidance and cell migration. In this study, we determined that TRIO plays a role in the novel pathways in Echo30 induced neuronal cell death. CONCLUSIONS/SIGNIFICANCE: Our finding shows that TRIO plays a critical role in neuronal cell death by Echo30 infection. Echo30 infection activates TRIO-guanine nucleotide exchange factor (GEF) domains (GEFD2) and RhoA signaling in turn. These results suggest that Echo30 infection induced neuronal cell death by activation of the TRIO-RhoA signaling. We expect the regulation of TRIO-RhoA signaling may represent a new therapeutic approach in treating aseptic meningitis and encephalitis induced by Echo30.


Assuntos
Morte Celular , Infecções por Echovirus , Enterovirus Humano B , Fatores de Troca do Nucleotídeo Guanina , Proteínas Serina-Treonina Quinases , Proteína rhoA de Ligação ao GTP , Morte Celular/genética , Linhagem Celular Tumoral , Infecções por Echovirus/genética , Infecções por Echovirus/metabolismo , Enterovirus Humano B/genética , Enterovirus Humano B/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Humanos , Neuroblastoma , Neurônios/metabolismo , Óxido Nítrico/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Ativação Transcricional , Proteína rhoA de Ligação ao GTP/antagonistas & inibidores , Proteína rhoA de Ligação ao GTP/genética , Proteína rhoA de Ligação ao GTP/metabolismo
4.
Ann Biol Clin (Paris) ; 70(2): 189-98, 2012.
Artigo em Francês | MEDLINE | ID: mdl-22484530

RESUMO

The aim of the present work was to assess the genetic and antigenic variability in the VP1 region of type 3 echviruses (E-3), an enterovirus serotype associated to meningitis, neuro-muscular diseases and type 1 diabetes in human. Forty-six VP1 sequences of E-3, among which 9 were isolated in tunisian infants, were included. Phylogenetic analyses and nucleotidic divergence rates were studied in the complete VP1 region and in a 290-nucleotides fragment in the 5' part of the P1. Aminoacid sequences were deduced in the aim to identify genotype-specific antigenetic determinants. E-3 sequences divided into two genogroups, I and II; the genetic variability within the E-3 serotype reached 29.1%. Genogroup I included sequences with a relatively high genetic diversity among each other, some of them grouped in one genotype with at most 15.1% divergence rate. The sequences included in Genogroup II have a maximum of 13.8% divergence corresponding probably to only one genotype. The two genogroups have a concomitant circulation and a wide geographical and temporal distribution. Aminoacid substitutions that may be specific to genogroups, genotypes and special variant were noted. This work provides a first tentative of classification of E-3 into genogroups and genotypes and reports new E-3 sequences from North Africa. It contributes to a better understanding of the molecular epidemiology of human enteroviruses, and of Echoviruses type 3 in particular, a serotype that remains insufficiently studied in the international literature.


Assuntos
Infecções por Echovirus/virologia , Enterovirus Humano B/genética , Variação Genética , Sequência de Aminoácidos , Criança , Pré-Escolar , Infecções por Echovirus/genética , Enterovirus Humano B/classificação , Enterovirus Humano B/isolamento & purificação , Genoma Viral/genética , Humanos , Lactente , Dados de Sequência Molecular , Filogenia , Análise de Sequência de RNA , Homologia de Sequência de Aminoácidos , Tunísia , Proteínas Estruturais Virais/análise , Proteínas Estruturais Virais/genética
5.
Vopr Virusol ; 56(6): 37-42, 2011.
Artigo em Russo | MEDLINE | ID: mdl-22359948

RESUMO

In 2009 echovirus 9 caused a higher seasonal incidence of enterovirus infection (EVI) and its several outbreaks in a number of regions of Russia. Analysis of the partial VP1 coding region differentiated 4 phylogenetic lineages of echoviruses 9 variants identified in patients with aseptic meningitis and EVI in 2007-2009. One variant of echovirus 9 was most commonly encountered in 2009. Echoviruses 9 identified in different areas, which had a high (98.2-100%) homology of nucleotide sequences of the partial VP1 coding region, varied in the amino acid sequences within the B-C loop.


Assuntos
Proteínas do Capsídeo/genética , Echovirus 9/genética , Infecções por Echovirus , Meningite Asséptica , Homologia de Sequência do Ácido Nucleico , Surtos de Doenças , Infecções por Echovirus/epidemiologia , Infecções por Echovirus/genética , Infecções por Echovirus/virologia , Genoma Viral/genética , Humanos , Meningite Asséptica/epidemiologia , Meningite Asséptica/genética , Meningite Asséptica/virologia , Dados de Sequência Molecular , Filogenia , Federação Russa/epidemiologia , Homologia de Sequência de Aminoácidos
6.
Virus Res ; 139(1): 32-8, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19013201

RESUMO

Echovirus 11 (E-11) has been one of the most frequently discovered human enterovirus (HEV) in Finland during the past few years. We have studied molecular epidemiological patterns of E-11 from 1993 to 2007 exploiting the 257-nucleotide region in the 5'-part of the VP1 used for genetic typing of HEV. Designated genogroup D strains had a striking prevalence among the Finnish strains, a finding in accordance with the recent data from other geographical regions. The subgroup D4, harboring the oldest strains, had become extinct in the beginning of the millennium and D5 strains had taken over. Similarly, a new subgroup of D5 had started to diverge from the main D5 in 2006. However, in addition to endemic D strains, few single strains clustered also to genogroups A and C suggesting importation from more distant locations. The relatively large amino acid sequence variability between and within the genogroups favored the idea of antigenic differences. Neutralization assays confirmed that antigenic differences existed, although all studied E-11 strains were neutralized with antisera against the prototype strain Gregory. Five of the six studied strains belonging to genogroup D were, unexpectedly, also neutralized with antisera against coxsackievirus A9 Griggs.


Assuntos
Antígenos Virais/imunologia , Infecções por Echovirus/virologia , Enterovirus Humano B/classificação , Enterovirus Humano B/genética , Animais , Anticorpos Antivirais/sangue , Variação Antigênica , Antígenos Virais/genética , Linhagem Celular , Linhagem Celular Tumoral , Infecções por Echovirus/genética , Infecções por Echovirus/imunologia , Enterovirus Humano B/isolamento & purificação , Finlândia/epidemiologia , Humanos , Epidemiologia Molecular , Dados de Sequência Molecular , Testes de Neutralização , Filogenia , Sorotipagem , Esgotos/virologia
7.
Ann Neurol ; 49(2): 249-53, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11221802

RESUMO

The role of enteroviruses in pathogenesis of amyotrophic lateral sclerosis (ALS) is controversial. A recent study, based on reverse transcription-polymerase chain reaction (RT-PCR) analysis of spinal cord, reported identification of a novel echovirus in 15 of 17 French subjects with ALS and only 1 of 29 subjects with other neurologic diseases. We established a real-time RT-PCR method based on this novel echovirus sequence and used this method and that previously employed for analysis of the French subjects to determine the prevalence of echoviral sequences in spinal cord and motor cortex of sporadic ALS subjects from the United States. No echoviral sequences were found in 20 spinal cord and 10 motor cortex samples from autopsy-confirmed cases of ALS or 13 spinal cord and 5 motor cortex samples from subjects with no motor neuron disease.


Assuntos
Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Encéfalo/patologia , Infecções por Echovirus/genética , Enterovirus Humano B/genética , Medula Espinal/patologia , Adulto , Idoso , Sequência de Bases , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase/métodos
10.
Jpn J Microbiol ; 19(3): 201-9, 1975 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-1165613

RESUMO

A continuing surveillance on enterovirus infection in healthy infants was conducted from October 1971 through February 1973 in urban areas in Ghana, West Africa. About 40 infants were visited in every two months for collection of faecal specimens and examined for infection. Enteroviruses were recovered in tissue culture. The overall isolation rate of enteroviruses was approximately 44%, and there was no seasonal difference between rainy and dry seasons. The rate of virus isolation in urban areas was significantly higher than in rural areas. Within the urban areas, however, no difference in the rate of virus isolation was detected between densely populated and sparsely populated areas. The results of virus identification revealed that all three types of Poliovirus, many types of Echovirus and a few Coxsackieviruses were isolated during the course of the study. It was observed that improvement of sanitary facilities decreased the frequency of virus infection among infants, but the condition of water supply did not influence the virus infection rate. Neither the age of infants nor the size of siblings showed any relation to the virus isolation rate. It was suggested from the results that many types of enteroviruses have been circulation continuously in the tropical urban community throughout the year.


Assuntos
Infecções por Enterovirus/epidemiologia , Infecções por Coxsackievirus/epidemiologia , Infecções por Coxsackievirus/genética , Infecções por Coxsackievirus/transmissão , Infecções por Echovirus/epidemiologia , Infecções por Echovirus/genética , Infecções por Echovirus/transmissão , Infecções por Enterovirus/genética , Infecções por Enterovirus/transmissão , Fezes/microbiologia , Gana , Humanos , Lactente , Poliomielite/epidemiologia , Poliomielite/genética , Poliomielite/transmissão , Vigilância da População , Estações do Ano , Banheiros , População Urbana , Microbiologia da Água , Abastecimento de Água
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