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1.
Hum Genomics ; 18(1): 14, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321488

RESUMO

BACKGROUND: Periodic bioinformatics-based screening of wastewater for assessing the diversity of potential human viral pathogens circulating in a given community may help to identify novel or potentially emerging infectious diseases. Any identified contigs related to novel or emerging viruses should be confirmed with targeted wastewater and clinical testing. RESULTS: During the COVID-19 pandemic, untreated wastewater samples were collected for a 1-year period from the Great Lakes Water Authority Wastewater Treatment Facility in Detroit, MI, USA, and viral population diversity from both centralized interceptor sites and localized neighborhood sewersheds was investigated. Clinical cases of the diseases caused by human viruses were tabulated and compared with data from viral wastewater monitoring. In addition to Betacoronavirus, comparison using assembled contigs against a custom Swiss-Prot human virus database indicated the potential prevalence of other pathogenic virus genera, including: Orthopoxvirus, Rhadinovirus, Parapoxvirus, Varicellovirus, Hepatovirus, Simplexvirus, Bocaparvovirus, Molluscipoxvirus, Parechovirus, Roseolovirus, Lymphocryptovirus, Alphavirus, Spumavirus, Lentivirus, Deltaretrovirus, Enterovirus, Kobuvirus, Gammaretrovirus, Cardiovirus, Erythroparvovirus, Salivirus, Rubivirus, Orthohepevirus, Cytomegalovirus, Norovirus, and Mamastrovirus. Four nearly complete genomes were recovered from the Astrovirus, Enterovirus, Norovirus and Betapolyomavirus genera and viral species were identified. CONCLUSIONS: The presented findings in wastewater samples are primarily at the genus level and can serve as a preliminary "screening" tool that may serve as indication to initiate further testing for the confirmation of the presence of species that may be associated with human disease. Integrating innovative environmental microbiology technologies like metagenomic sequencing with viral epidemiology offers a significant opportunity to improve the monitoring of, and predictive intelligence for, pathogenic viruses, using wastewater.


Assuntos
Enterovirus , Viroses , Vírus , Humanos , Águas Residuárias , Michigan , Pandemias
2.
J Med Virol ; 96(2): e29449, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38314919

RESUMO

Enterovirus C99 (EV-C99) is a newly identified EV serotype within the species Enterovirus C. Few studies on EV-C99 have been conducted globally. More information and research on EV-C99 are needed to assess its genetic characteristics, phylogenetic relationships, and associations with enteroviral diseases. Here, the phylogenetic characteristics of 11 Chinese EV-C99 strains have been reported. The full-length genomic sequences of these 11 strains show 79.4-80.5% nucleotide identity and 91.7-94.3% amino acid (aa) identity with the prototype EV-C99. A maximum likelihood phylogenetic tree constructed based on the entire VP1 coding region identified 13 genotypes (A-M), revealing a high degree of variation among the EV-C99 strains. Phylogeographic analysis showed that the Xinjiang Uygur Autonomous Region is an important source of EV-C99 epidemics in various regions of China. Recombination analysis revealed inter-serotype recombination events of 16 Chinese EV-C99 strains in 5' untranslated regions and 3D regions, resulting in the formation of a single recombination form. Additionally, the Chinese strain of genotype J showed rich aa diversity in the P1 region, indicating that the genotype J of EV-C99 is still going through variable dynamic changes. This study contributes to the global understanding of the EV-C99 genome sequence and holds substantial implications for the surveillance of EV-C99.


Assuntos
Infecções por Enterovirus , Enterovirus , Humanos , Enterovirus/genética , Filogenia , Infecções por Enterovirus/epidemiologia , China/epidemiologia , Genótipo , Genoma Viral
3.
Influenza Other Respir Viruses ; 18(2): e13250, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38314065

RESUMO

Background: Respiratory viral infections are common in febrile infants ≤90 days. However, the detection of viruses other than enterovirus in the blood and cerebrospinal fluid (CSF) of young infants is not well defined. We sought to quantify the occurrence of respiratory viruses in the blood and CSF of febrile infants ≤90 days. Methods: We conducted a nested cohort study examining plasma and CSF samples from febrile infants 15-90 days via rtPCR. The samples were tested for respiratory viruses (respiratory syncytial virus, influenza, enterovirus, parechovirus, adenovirus, bocavirus). Clinical and laboratory data were also collected to determine the presence of serious bacterial infections (SBI). Results: Twenty-four percent (30 of 126) of infants had plasma/CSF specimens positive for a respiratory virus. Enterovirus and parechovirus were the most commonly detected respiratory viruses. Viral positivity was highest in plasma samples at 25% (27 of 107) compared with CSF samples at 15% (nine of 62). SBIs (specifically urinary tract infections) were less common in infants with a sample positive for a respiratory virus compared to those without a virus detected (3% vs. 26%, p = 0.008). Conclusions: Our findings support the use of molecular diagnostics to include the identification of parechovirus in addition to enterovirus in febrile infants ≤90 days. Additionally, these data support the utilization of blood specimens to diagnose enterovirus and parechovirus infections in febrile infants ≤90 days.


Assuntos
Infecções por Enterovirus , Enterovirus , Infecções por Picornaviridae , Vírus Sincicial Respiratório Humano , Vírus , Lactente , Humanos , Estudos de Coortes , Vírus/genética , Infecções por Enterovirus/epidemiologia , Enterovirus/genética , Antígenos Virais , Febre/diagnóstico , Infecções por Picornaviridae/epidemiologia
4.
J Med Virol ; 96(2): e29471, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38353496

RESUMO

Human enteroviruses (EV) are the most common cause of aseptic meningitis worldwide. Data on EV viral load in cerebrospinal fluid (CSF) and related epidemiological studies are scarce in Brazil. This study investigated the influence of EV viral load on CSF parameters, as well as identifying the involved species. CSF samples were collected in 2018-2019 from 140 individuals at The Hospital das Clínicas, São Paulo. The EV viral load was determined using real-time quantitative polymerase chain reaction, while EV species were identified by 5'UTR region sequencing. Median viral load was 5.72 log10 copies/mL and did not differ by subjects' age and EV species. Pleocytosis was observed in 94.3% of cases, with the highest white blood cell (WBC) counts in younger individuals. Viral load and WBC count were correlated in children (p = 0.0172). Elevated lactate levels were observed in 60% of cases and correlated with the viral load in preteen-teenagers (p = 0.0120) and adults (p = 0.0184). Most individuals had normal total protein levels (70.7%), with higher in preteen-teenagers and adults (p < 0.0001). By sequencing, 8.2% were identified as EV species A and 91.8% as species B. Age-specific variations in CSF characteristics suggest distinct inflammatory responses in each group.


Assuntos
Infecções por Enterovirus , Enterovirus , Meningite Asséptica , Meningite Viral , Criança , Adulto , Adolescente , Humanos , Lactente , Enterovirus/genética , Meningite Asséptica/líquido cefalorraquidiano , Brasil/epidemiologia , Estudos Retrospectivos , Líquido Cefalorraquidiano
5.
BMC Infect Dis ; 24(1): 205, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360603

RESUMO

Hand foot and mouth disease (HFMD) is caused by a variety of enteroviruses, and occurs in large outbreaks in which a small proportion of children deteriorate rapidly with cardiopulmonary failure. Determining which children are likely to deteriorate is difficult and health systems may become overloaded during outbreaks as many children require hospitalization for monitoring. Heart rate variability (HRV) may help distinguish those with more severe diseases but requires simple scalable methods to collect ECG data.We carried out a prospective observational study to examine the feasibility of using wearable devices to measure HRV in 142 children admitted with HFMD at a children's hospital in Vietnam. ECG data were collected in all children. HRV indices calculated were lower in those with enterovirus A71 associated HFMD compared to those with other viral pathogens.HRV analysis collected from wearable devices is feasible in a low and middle income country (LMIC) and may help classify disease severity in HFMD.


Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Doença de Mão, Pé e Boca , Criança , Humanos , Lactente , Doença de Mão, Pé e Boca/diagnóstico , Frequência Cardíaca , Estudos de Viabilidade , China/epidemiologia
6.
Sci Adv ; 10(7): eadg3060, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363831

RESUMO

Selective pressures on viruses provide opportunities to establish target site specificity and mechanisms of antivirals. Enterovirus (EV)-A71 with resistant mutations in the stem loop (SL) II internal ribosome entry site (IRES) (SLIIresist) were selected at low doses of the antiviral dimethylamiloride (DMA)-135. The EV-A71 mutants were resistant to DMA-135 at concentrations that inhibit replication of wild-type virus. EV-A71 IRES structures harboring resistant mutations induced efficient expression of Luciferase messenger RNA in the presence of noncytotoxic doses of DMA-135. Nuclear magnetic resonance indicates that the mutations change the structure of SLII at the binding site of DMA-135 and at the surface recognized by the host protein AU-rich element/poly(U)-binding/degradation factor 1 (AUF1). Biophysical studies of complexes formed between AUF1, DMA-135, and either SLII or SLIIresist show that DMA-135 stabilizes a ternary complex with AUF1-SLII but not AUF1-SLIIresist. This work demonstrates how viral evolution elucidates the (DMA-135)-RNA binding site specificity in cells and provides insights into the viral pathways inhibited by the antiviral.


Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Humanos , Enterovirus/genética , Enterovirus/metabolismo , Infecções por Enterovirus/tratamento farmacológico , Infecções por Enterovirus/genética , Infecções por Enterovirus/metabolismo , Replicação Viral , Antígenos Virais , RNA Viral/metabolismo , Antivirais/farmacologia
7.
Int J Mol Sci ; 25(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339075

RESUMO

Recent research suggests that T-cell receptor (TCR) sequences expanded during human immunodeficiency virus and SARS-CoV-2 infections unexpectedly mimic these viruses. The hypothesis tested here is that TCR sequences expanded in patients with type 1 diabetes mellitus (T1DM) and autoimmune myocarditis (AM) mimic the infectious triggers of these diseases. Indeed, TCR sequences mimicking coxsackieviruses, which are implicated as triggers of both diseases, are statistically significantly increased in both T1DM and AM patients. However, TCRs mimicking Clostridia antigens are significantly expanded in T1DM, whereas TCRs mimicking Streptococcal antigens are expanded in AM. Notably, Clostridia antigens mimic T1DM autoantigens, such as insulin and glutamic acid decarboxylase, whereas Streptococcal antigens mimic cardiac autoantigens, such as myosin and laminins. Thus, T1DM may be triggered by combined infections of coxsackieviruses with Clostridia bacteria, while AM may be triggered by coxsackieviruses with Streptococci. These TCR results are consistent with both epidemiological and clinical data and recent experimental studies of cross-reactivities of coxsackievirus, Clostridial, and Streptococcal antibodies with T1DM and AM antigens. These data provide the basis for developing novel animal models of AM and T1DM and may provide a generalizable method for revealing the etiologies of other autoimmune diseases. Theories to explain these results are explored.


Assuntos
Doenças Autoimunes , Infecções por Coxsackievirus , Diabetes Mellitus Tipo 1 , Enterovirus , Miocardite , Infecções Estreptocócicas , Animais , Humanos , Doenças Autoimunes/complicações , Infecções por Coxsackievirus/complicações , Autoantígenos , Streptococcus , Infecções Estreptocócicas/complicações , Antígenos de Bactérias , Receptores de Antígenos de Linfócitos T
8.
Sci Total Environ ; 918: 170519, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38316300

RESUMO

We report the presence of Echovirus 11 (E11) in wastewater in Sicily (Southern Italy), since August 2022. Overall, the 5.4 % of sewage samples (7/130) collected in 2022 were positives for E11 and then the percentage of E11-positive sewage samples reached the value of 27.27(18/66) in the first semester of 2023. Phylogenetic analysis of VP1 sequences showed for most E11-positive samples (16/25: 64 %) close genetic correlation (98.4-99.4 % nucleotide identity) to E11 lineage 1 strains involved in recently reported severe neonatal infections.


Assuntos
Enterovirus , Águas Residuárias , Humanos , Recém-Nascido , Esgotos , Sicília , Filogenia , Enterovirus Humano B/genética
9.
Front Cell Infect Microbiol ; 14: 1302314, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38343888

RESUMO

Background: Japanese encephalitis (JE) is a notifiable infectious disease in China. Information on every case of JE is reported to the superior health administration department. However, reported cases include both laboratory-confirmed and clinically diagnosed cases. This study aimed to differentiate between clinical and laboratory-confirmed cases of Japanese encephalitis virus (JEV) infection, and improve the accuracy of reported JE cases by analyzing the acute-phase serum and cerebrospinal fluid of all reported JE cases in the Sichuan province from 2012 to 2022. Methods: All acute-phase serum and/or cerebrospinal fluid samples of the reported JE cases were screened for IgM(ImmunoglobulinM)to JEV using the enzyme-linked immunosorbent assay (ELISA), and the detection of the viral genes of JEV and 9 other pathogens including enterovirus (EV), using reverse transcription PCR was attempted. Epidemiological analyses of JE and non-JE cases based on sex, age, onset time, and geographical distribution were also performed. Results: From 2012 to 2022, 1558 JE cases were reported in the Sichuan province. The results of serological (JEV-specific IgM) and genetic testing for JEV showed that 81% (1262/1558) of the reported cases were confirmed as JEV infection cases (laboratory-confirmed cases). Among the 296 cases of non-JEV infection, 6 viruses were detected in the cerebrospinal fluid in 62 cases, including EV and the Epstein-Barr virus (EBV), constituting 21% (62/296) of all non-JE cases. Among the 62 non-JEV infection cases with confirmed pathogens, infections with EV and EBV included 17 cases each, herpes simplex virus (HSV-1/2) included 14 cases, varicella- zoster virus included 6 cases, mumps virus included 2 cases, and human herpes viruses-6 included 1 case. Additionally, there were five cases involving mixed infections (two cases of EV/EBV, one case of HSV-1/HSV-2, one case of EBV/HSV-1, and one case of EV/herpes viruses-6). The remaining 234 cases were classified as unknown viral encephalitis cases. Our analysis indicated that those aged 0-15 y were the majority of the patients among the 1558 reported JE cases. However, the incidence of laboratory-confirmed JE cases in the >40 y age group has increased in recent years. The temporal distribution of laboratory-confirmed cases of JE revealed that the majority of cases occurred from May to September each year, with the highest incidence in August. Conclusion: The results of this study indicate that there is a certain discrepancy between clinically diagnosed and laboratory-confirmed cases of JE. Each reported case should be based on laboratory detection results, which is of great importance in improving the accuracy of case diagnosis and reducing misreporting. Our results are not only important for addressing JE endemic to the Sichuan province, but also provide a valuable reference for the laboratory detection of various notifiable infectious diseases in China and other regions outside China.


Assuntos
Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Infecções por Enterovirus , Enterovirus , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 1 , Humanos , Adulto , Encefalite Japonesa/diagnóstico , Encefalite Japonesa/epidemiologia , Vírus da Encefalite Japonesa (Espécie)/genética , Herpesvirus Humano 4 , Anticorpos Antivirais , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/epidemiologia , Imunoglobulina M , Herpesvirus Humano 2
10.
PLoS Pathog ; 20(1): e1011967, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38271479

RESUMO

Given the serious neurological complications and deaths associated with enterovirus 71 (EV71) infection, there is an urgent need to develop effective antivirals against this viral infection. In this study, we demonstrated that two Cathelicidin-derived peptides, LL-18 and FF-18 were more potent against EV71 infection than the parent peptide LL-37, which is the mature and processed form of Cathelicidin. These peptides could directly bind to the EV71 virus particles, but not to coxsackievirus, indicative of their high specificity. The binding of peptides with the virus surface occupied the viral canyon region in a way that could block virus-receptor interactions and inhibit viral uncoating. In addition, these peptide analogues could also relieve the deleterious effect of EV71 infection in vivo. Therefore, Cathelicidin-derived peptides might be excellent candidates for further development of antivirals to treat EV71 infection.


Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Humanos , Catelicidinas/farmacologia , Internalização do Vírus , Antivirais/metabolismo
11.
Emerg Microbes Infect ; 13(1): 2307514, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38240287

RESUMO

Enterovirus A71 (EV-A71) is the main pathogen causing hand, foot and mouth disease (HFMD) in children and occasionally associated with neurological diseases such as aseptic meningitis, brainstem encephalitis (BE) and acute flaccid paralysis. We report here that cellular pseudokinase tribbles 3 (TRIB3) facilitates the infection of EV-A71 via dual mechanisms. In one hand, TRIB3 maintains the metabolic stability of scavenger receptor class B member 2 (SCARB2), the bona fide receptor of EV-A71, to enhance the infectious entry and spreading of the virus. On the other hand, TRIB3 facilitates the replication of EV-A71 RNA in a SCARB2-independent manner. The critical role of TRIB3 in EV-A71 infection and pathogenesis was further demonstrated in vivo in mice. In comparison to wild-type C57BL/6 mice, EV-A71 infection in TRIB3 knockdown mice (Trib3+/-) resulted in significantly lower viral loads in muscular tissues and reduced lethality and severity of clinical scores and tissue pathology. In addition, TRIB3 also promoted the replication of coxsackievirus B3 (CVB3) and coxsackievirus A16 (CVA16) in vitro. In conclusion, our results suggest that TRIB3 is one of key host cellular proteins required for the infection and pathogenesis of EV-A71 and some other human enteroviruses and may thus be a potential therapeutic target for combating the infection of those viruses.


Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Doença de Mão, Pé e Boca , Animais , Criança , Humanos , Camundongos , Enterovirus/genética , Enterovirus Humano A/genética , Infecções por Enterovirus/complicações , Doença de Mão, Pé e Boca/complicações , Camundongos Endogâmicos C57BL
12.
J Med Virol ; 96(1): e29323, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38164047

RESUMO

Enteroviruses (EVs), single-stranded, positive-sense RNA viruses, can be classified into four species (A-D), which have previously been linked to a diverse range of disease manifestations and infections affecting the central nervous system. In the Enterovirus species B (EV-B), Echovirus type 11 (E11) has been observed to occasionally circulate in Taiwan, which was responsible for an epidemic of enterovirus infections in 2018. Here, 48 clinical specimens isolated in 2003, 2004, 2009, and 2018 were collected for the high-throughput sequencing. Notably, we identified 2018 Taiwanese strains having potential recombinations in the 3D gene, as well as one 2003 strain having a double recombination with E6 and Coxsackievirus B5 in the P2 and P3 regions, respectively. Additionally, one amino acid signature mutated from the Histidine (H) in throat swab specimens to the Tyrosine (Y) in cerebral spinal fluid specimens was detected at position 1496 (or 57) of the genomic coordinate (or 3A gene) to further demonstrate intra-host evolution in different organs. In conclusion, this study identifies potential intertypic recombination events and an intra-host signature mutation in E11 strains, isolated during a 2018 neurological disease outbreak in Taiwan, contributing to our understanding of its evolution and pathogenesis.


Assuntos
Infecções por Enterovirus , Enterovirus , Humanos , Filogenia , Enterovirus Humano B/genética , Enterovirus/genética , Infecções por Enterovirus/epidemiologia , Recombinação Genética
13.
J Med Virol ; 96(1): e29412, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38258311

RESUMO

Nonpharmaceutical interventions (NPIs) for coronavirus disease 2019 (COVID-19) not only reduce the prevalence of this disease among children but also influence the transmission of other viruses. This retrospective study investigated the impact of NPIs on human enterovirus (HEV) infection in children diagnosed with hand, foot, and mouth disease (HFMD) or herpangina (HA) in Hangzhou, China. We collected and analyzed the laboratory results and clinical data of children diagnosed with HFMD or HA during the following periods: pre-COVID-19 (January 2019 to December 2019), the COVID-19 pandemic (January 2020 to December 2022), and post-COVID-19 (January to December 2023). A total of 41 742 specimens that met the inclusion criteria were obtained, of which 1998 (4.79%) tested positive for enterovirus. In comparison to those in the pre-COVID-19 period, which had 695 (5.63%) HEV-positive specimens, the numbers dramatically decreased to 69 (1.19%), 398 (5.12%), and 112 (1.58%) in 2020, 2021, and 2022, respectively, but significantly increased to 724 (8.27%) in 2023. Seasonal peaks of infections occurred in May, June, July, and August each year, with the total detection rate ranging from 2019 to 2023 being 9.41% in May, 22.47% in June, 28.23% in July, and 12.16% in August, respectively. The difference in the detection rates of HEV infection between males and females was statistically significant (p < 0.005), with 5.11% (1221/23 898) of males and 4.35% (777/17 844) of females testing positive, resulting in a male-to-female positive ratio of 1.57:1. Among the age groups, 11.25% (378/3360) of the children aged 3-5 years had the highest detection rate, which steadily decreased with increasing or decreasing age. The detection of HEV indicated that >95% of the viruses were other types than the previously commonly reported enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16). In conclusion, NPIs for COVID-19 may be effective at reducing the transmission of HEV. However, with the relaxation of NPIs, the detection rate of HEVs increased slowly to a certain extent. Active awareness and surveillance of the epidemiological characteristics of HEV are essential for preventing, controlling, and managing the development of HFMD and HA, as well as contributing to the development of a multivalent HFMD vaccine.


Assuntos
COVID-19 , Infecções por Enterovirus , Enterovirus , Humanos , Feminino , Masculino , Criança , Pandemias , Estudos Retrospectivos , COVID-19/epidemiologia , Infecções por Enterovirus/epidemiologia , Antígenos Virais , China/epidemiologia
14.
Sci Rep ; 14(1): 2161, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-38272942

RESUMO

Enterovirus D68 (EV-D68) is an emerging pathogen that has caused outbreaks of severe respiratory disease worldwide, especially in children. We aim to investigate the prevalence and genetic characteristics of EV-D68 in children from Shanghai. Nasopharyngeal swab or bronchoalveolar lavage fluid samples collected from children hospitalized with community-acquired pneumonia were screened for EV-D68. Nine of 3997 samples were EV-D68-positive. Seven of nine positive samples were sequenced and submitted to GenBank. Based on partial polyprotein gene (3D) or complete sequence analysis, we found the seven strains belong to different clades and subclades, including three D1 (detected in 2013 and 2014), one D2 (2013), one D3 (2019), and two B3 (2014 and 2018). Overall, we show different clades and subclades of EV-D68 spread with low positive rates (0.2%) among children in Shanghai between 2013 and 2020. Amino acid mutations were found in the epitopes of the VP1 BC and DE loops and C-terminus; similarity analysis provided evidence for recombination as an important mechanism of genomic diversification. Both single nucleotide mutations and recombination play a role in evolution of EV-D68. Genetic instability within these clinical strains may indicate large outbreaks could occur following cumulative mutations.


Assuntos
Enterovirus Humano D , Infecções por Enterovirus , Enterovirus , Infecções Respiratórias , Criança , Humanos , Epidemiologia Molecular , Enterovirus Humano D/genética , Infecções Respiratórias/epidemiologia , Infecções por Enterovirus/epidemiologia , Filogenia , China/epidemiologia , Surtos de Doenças , Enterovirus/genética
15.
Virology ; 591: 109989, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38219371

RESUMO

Enteroviruses (EVs), comprise a genus in the Picornaviridae family, which have been shown to be neurotropic and can cause various neurological disorders or long-term neurological condition, placing a huge burden on society and families. The blood-brain barrier (BBB) is a protective barrier that prevents dangerous substances from entering the central nervous system (CNS). Recently, numerous EVs have been demonstrated to have the ability to disrupt BBB, and further lead to severe neurological damage. However, the precise mechanisms of BBB disruption associated with these EVs remain largely unknown. In this Review, we focus on the molecular mechanisms of BBB dysfunction caused by EVs, emphasizing the invasiveness of enterovirus A71 (EVA71), which will provide a research direction for further treatment and prevention of CNS disorders.


Assuntos
Infecções por Enterovirus , Enterovirus , Humanos , Barreira Hematoencefálica , Enterovirus/fisiologia , Sistema Nervoso Central , Transporte Biológico
16.
FASEB J ; 38(2): e23430, 2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38243751

RESUMO

Intestinal tuft cells, a kind of epithelial immune cells, rapidly expand in response to pathogenic infections, which is associated with infection-induced interleukin 25 (IL-25) upregulation. However, the metabolic mechanism of IL-25-induced tuft cell expansion is largely unknown. Folate metabolism provides essential purine and methyl substrates for cell proliferation and differentiation. Thus, we aim to investigate the roles of folate metabolism playing in IL-25-induced tuft cell expansion by enteroviral infection and recombinant murine IL-25 (rmIL-25) protein-stimulated mouse models. At present, enteroviruses, such as EV71, CVA16, CVB3, and CVB4, upregulated IL-25 expression and induced tuft cell expansion in the intestinal tissues of mice. However, EV71 did not induce intestinal tuft cell expansion in IL-25-/- mice. Interestingly, compared to the mock group, folate was enriched in the intestinal tissues of both the EV71-infected group and the rmIL-25 protein-stimulated group. Moreover, folate metabolism supported IL-25-induced tuft cell expansion since both folate-depletion and anti-folate MTX-treated mice had a disrupted tuft cell expansion in response to rmIL-25 protein stimulation. In summary, our data suggested that folate metabolism supported intestinal tuft cell expansion in response to enterovirus-induced IL-25 expression, which provided a new insight into the mechanisms of tuft cell expansion from the perspective of folate metabolism.


Assuntos
Infecções por Enterovirus , Ácido Fólico , Animais , Camundongos , Proliferação de Células , Enterovirus/metabolismo , Infecções por Enterovirus/metabolismo , Interleucina-17/metabolismo , Ácido Fólico/farmacologia
17.
BMC Health Serv Res ; 24(1): 59, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212779

RESUMO

BACKGROUND: A Meningitis and Encephalitis Surveillance (MERIN) was implemented in 2003 in Lower Saxony, Germany as an alternative to acute flaccid paralyses surveillance, as the latter did not reach WHO sensitivity criteria. The system provides information on circulating enterovirus (EV) serotypes by focussing on patients with suspected aseptic meningitis, encephalitis or acute flaccid paralysis and contributes to the national surveillance in documenting polio free status. MERIN is based on voluntary participation of hospitals. Therefore, our evaluation focusses on acceptability of the system's objectives and performance, and identifying areas for improvement. METHODS: To assess acceptability, 32 contributing hospitals were invited to an online-based survey (11/2021 to 01/2022) to rate the MERIN objectives, laboratory's performance, their workload, modes of processes and communication. Ideas for improvement were collected in open fields. In addition, data completeness and timeliness of laboratory diagnostics were assessed. RESULTS: Of 32 hospitals, 21 responded (66% response rate), sending 30 questionnaires, 25 from pediatric and 5 from neurological departments. High levels of satisfaction with the communication (≥ 96%), timeliness (≥ 81%), and distribution of the results (≥ 85%) were reported, 97% of participants judged the required workload as adequate. The median proportion of eligible patients included in MERIN was 75%. Participants gave rapid and reliable diagnostic testing the highest priority (96%), while monitoring of Germany's polio-free status was rated the lowest (61%). Providing medical reports digitally as well as regular updates about circulating EV serotypes were identified as areas for improvement. Data completeness of selected variables ranged from 78.3 to 99.9%. Median time between sample collection and arrival at laboratory was 2 days [IQR 1-3], EV diagnostics via PCR took one day [IQR 0-6] and EV isolation on cell culture 11 days [IQR 10-13]. CONCLUSION: MERIN is a highly accepted surveillance system. Its quality was enhanced further by addressing the suggested improvements such as regular reports on circulating EV serotypes and facilitating digital access to laboratory results. Our results emphasise the importance of recognizing and considering participants' motivations and expectations, and addressing their priorities, even if this is not the surveillance system's main focus. This approach can be applied to surveillance systems of other non-mandatory notifiable diseases.


Assuntos
Encefalite , Infecções por Enterovirus , Enterovirus , Meningite , Poliomielite , Humanos , Criança , Infecções por Enterovirus/diagnóstico , Infecções por Enterovirus/epidemiologia , Meningite/diagnóstico , Meningite/epidemiologia , Poliomielite/epidemiologia , Encefalite/epidemiologia , Alemanha/epidemiologia , Inquéritos e Questionários , Vigilância da População/métodos
18.
Medicine (Baltimore) ; 103(1): e36797, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38181280

RESUMO

RATIONALE: Hand-foot-mouth disease (HFMD) caused by Enterovirus A71, complicated by cardiopulmonary failure, is associated with a high mortality rate despite intensive treatment. To date, there is a paucity of clinical management data, regarding the use of extracorporeal life support (VA-ECMO) for Enterovirus-A71 associated cardiopulmonary failure reported. PATIENT CONCERNS: The patient in this study presented with severe HFMD complicated by cardiopulmonary failure, polymorphic ventricular tachycardia, and cardiac arrest. DIAGNOSES: Clinical presentations, laboratory data, and polymerase chain reaction (PCR) results from rectal swabs were used to confirm the diagnosis of severe HFMD caused by Enterovirus A71. INTERVENTIONS: The patient was managed with chest compression and an automatic external defibrillator, mechanical ventilation, intravenous immunoglobulin (IVIG), continuous renal replacement therapy (CRRT) and inotrope (milrinone). The patient did not respond to these interventions and subsequently required further management with VA-ECMO. OUTCOMES: The patient achieved a favorable outcomes. LESSONS: Our study highlights that extracorporeal membrane oxygenation and CRRT can enhance the survival outcomes of patients with severe HFMD with cardiopulmonary failure complications. Furthermore, we propose specific indications for the initiation of VA-ECMO.


Assuntos
Terapia de Substituição Renal Contínua , Infecções por Enterovirus , Enterovirus , Oxigenação por Membrana Extracorpórea , Doença de Mão, Pé e Boca , Humanos , Infecções por Enterovirus/complicações , Infecções por Enterovirus/terapia , Doença de Mão, Pé e Boca/complicações , Doença de Mão, Pé e Boca/terapia , Antígenos Virais
20.
J Virol ; 98(2): e0174923, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38189249

RESUMO

Enterovirus 71 (EV71) is one of the major pathogens causing hand, foot, and mouth disease in children under 5 years old, which can result in severe neurological complications and even death. Due to limited treatments for EV71 infection, the identification of novel host factors and elucidation of mechanisms involved will help to counter this viral infection. N-terminal acetyltransferase 6 (NAT6) was identified as an essential host factor for EV71 infection with genome-wide CRISPR/Cas9 screening. NAT6 facilitates EV71 viral replication depending on its acetyltransferase activity but has little effect on viral release. In addition, NAT6 is also required for Echovirus 7 and coxsackievirus B5 infection, suggesting it might be a pan-enterovirus host factor. We further demonstrated that NAT6 is required for Golgi integrity and viral replication organelle (RO) biogenesis. NAT6 knockout significantly inhibited phosphatidylinositol 4-kinase IIIß (PI4KB) expression and PI4P production, both of which are key host factors for enterovirus infection and RO biogenesis. Further mechanism studies confirmed that NAT6 formed a complex with its substrate actin and one of the PI4KB recruiters-acyl-coenzyme A binding domain containing 3 (ACBD3). Through modulating actin dynamics, NAT6 maintained the integrity of the Golgi and the stability of ACBD3, thereby enhancing EV71 infection. Collectively, these results uncovered a novel mechanism of N-acetyltransferase supporting EV71 infection.IMPORTANCEEnterovirus 71 (EV71) is an important pathogen for children under the age of five, and currently, no effective treatment is available. Elucidating the mechanism of novel host factors supporting viral infection will reveal potential antiviral targets and aid antiviral development. Here, we demonstrated that a novel N-acetyltransferase, NAT6, is an essential host factor for EV71 replication. NAT6 could promote viral replication organelle (RO) formation to enhance viral replication. The formation of enterovirus ROs requires numerous host factors, including acyl-coenzyme A binding domain containing 3 (ACBD3) and phosphatidylinositol 4-kinase IIIß (PI4KB). NAT6 could stabilize the PI4KB recruiter, ACBD3, by inhibiting the autophagy degradation pathway. This study provides a fresh insight into the relationship between N-acetyltransferase and viral infection.


Assuntos
Infecções por Coxsackievirus , Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Criança , Humanos , Pré-Escolar , 1-Fosfatidilinositol 4-Quinase/metabolismo , Enterovirus Humano A/fisiologia , Acetiltransferases N-Terminal/metabolismo , Biogênese de Organelas , Actinas/metabolismo , Proteínas de Membrana/metabolismo , Enterovirus/metabolismo , Antivirais , Coenzima A/metabolismo , Replicação Viral/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
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