Journal articles on the topic 'Enteroviru'
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Novikov, D. V., and D. A. Melentev. "Enteroviral (Picornaviridae: Enterovirus) (nonpolio) vaccines." Problems of Virology 67, no. 3 (July 13, 2022): 185–92. http://dx.doi.org/10.36233/0507-4088-111.
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Non-polio enteroviruses (NPEVs) are ubiquitous and are one of the main causative agents of viral infections in children. NPEVs most commonly infect newborns and young children, due to their lack of antibodies. In children, clinical manifestations can range from acute febrile illness to severe complications that require hospitalization and lead in some cases to disability or death. NPEV infections can have severe consequences, such as polio-like diseases, serous meningitis, meningoencephalitis, myocarditis, etc. The most promising strategy for preventing such diseases is vaccination. No less than 53 types of NPEVs have been found to circulate in Russia. However, of epidemic importance are the causative agents of exanthemic forms of the disease, aseptic meningitis and myocarditis. At the same time, the frequency of NPEV detection in the constituent entities of the Russian Federation is characterized by uneven distribution and seasonal upsurges. The review discusses the epidemic significance of different types of enteroviruses, including those relevant to the Russian Federation, as well as current technologies used to create enterovirus vaccines for the prevention of serious diseases.
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Kreuter, Justin D., Arti Barnes, James E. McCarthy, Joseph D. Schwartzman, M. Steven Oberste, C. Harker Rhodes, John F. Modlin, and Peter F. Wright. "A Fatal Central Nervous System Enterovirus 68 Infection." Archives of Pathology & Laboratory Medicine 135, no. 6 (June 1, 2011): 793–96. http://dx.doi.org/10.5858/2010-0174-cr.1.
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Abstract The anticipated eradication of poliovirus emphasizes the need to identify other enteroviral causes of severe central nervous system disease. Enterovirus 68 has been implicated only in cases of respiratory illness. We therefore report a case of fatal meningomyeloencephalitis caused by enterovirus 68 in a 5-year-old boy, which required neuropathology, microbiology, and molecular techniques to diagnose.
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Schlesinger, Yechiel, Mark H. Sawyer, and Gregory A. Storch. "Enteroviral Meningitis in Infancy: Potential Role for Polymerase Chain Reaction in Patient Management." Pediatrics 94, no. 2 (August 1, 1994): 157–62. http://dx.doi.org/10.1542/peds.94.2.157.
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Study objective. To evaluate the performance characteristics and potential clinical utility of a polymerase chain reaction (PCR) assay for enteroviral RNA in comparison to viral culture in infants under 3 months of age with meningitis. Specimens and testing. Specimens were obtained from a collection of cerebrospinal fluid specimens from infants under 3 months of age (excluding those in the neonatal intensive care unit) undergoing lumbar puncture at St. Louis Children's Hospital during a 12-month period. Those tested by PCR included all 27 with pleocytosis, 8 others from infants without pleocytosis but from whom an enterovirus was cultured, and 10 from infants who did not have pleocytosis and had a negative viral culture of cerebrospinal fluid. Viral cultures were performed at the discretion of physicians caring for individual patients. Results. PCR was positive for enteroviral RNA on cerebrospinal fluid (CSF) specimens from 11 of 12 patients with definite or probable enteroviral meningitis, as well as on 6 of 13 with possible enteroviral meningitis, and was negative on all 10 with absence of pleocytosis and negative enteroviral cultures. CSF viral cultures were negative in 6 of the patients in whom PCR was positive. Viral cultures had minimal impact on patient management. In contrast, under study assumptions, PCR could have saved an average of 1.2 days of hospitalization per patient in the 27 patients with CSF pleocytosis. Conclusions. Enterovirus PCR performed on CSF is a sensitive and specific method for the diagnosis of enteroviral meningitis. This method has the potential for improving the accuracy of diagnosis in young infants and for saving costs by allowing earlier diagnosis and discharge from the hospital when clinically appropriate.
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Huang, Ya-Ling, Sheng-Wen Huang, Chun-Yu Shen, Dayna Cheng, and Jen-Ren Wang. "Conserved Residues Adjacent to ß-Barrel and Loop Intersection among Enterovirus VP1 Affect Viral Replication: Potential Target for Anti-Enteroviral Development." Viruses 14, no. 2 (February 10, 2022): 364. http://dx.doi.org/10.3390/v14020364.
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Enterovirus genus has over one hundred genotypes and could cause several kinds of severe animal and human diseases. Understanding the role of conserved residues in the VP1 capsid protein among the enterovirus genus may lead to anti-enteroviral drug development. The highly conserved residues were found to be located at the loop and ß-barrel intersections. To elucidate the role of these VP1 residues among the enterovirus genus, alanine substitution reverse genetics (rg) variants were generated, and virus properties were investigated for their impact. Six highly conserved residues were identified as located near the inside of the canyon, and four of them were close to the ß-barrel and loop intersection. The variants rgVP1-R86A, rgVP1-P193A, rgVP1-G231A, and rgVP1-K256A were unable to be obtained, which may be due to disruption in the virus replication process. In contrast, rgVP1-E134A and rgVP1-P157A replicated well and rgVP1-P157A showed smaller plaque size, lower viral growth kinetics, and thermal instability at 39.5°C when compared to the rg wild type virus. These findings showed that the conserved residues located at the ß-barrel and loop junction play roles in modulating viral replication, which may provide a pivotal role for pan-enteroviral inhibitor candidate.
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Ianevski, Aleksandr, Eva Zusinaite, Tanel Tenson, Valentyn Oksenych, Wei Wang, Jan Egil Afset, Magnar Bjørås, and Denis E. Kainov. "Novel Synergistic Anti-Enteroviral Drug Combinations." Viruses 14, no. 9 (August 25, 2022): 1866. http://dx.doi.org/10.3390/v14091866.
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Background: Enterovirus infections affect people around the world, causing a range of illnesses, from mild fevers to severe, potentially fatal conditions. There are no approved treatments for enterovirus infections. Methods: We have tested our library of broad-spectrum antiviral agents (BSAs) against echovirus 1 (EV1) in human adenocarcinoma alveolar basal epithelial A549 cells. We also tested combinations of the most active compounds against EV1 in A549 and human immortalized retinal pigment epithelium RPE cells. Results: We confirmed anti-enteroviral activities of pleconaril, rupintrivir, cycloheximide, vemurafenib, remdesivir, emetine, and anisomycin and identified novel synergistic rupintrivir–vemurafenib, vemurafenib–pleconaril and rupintrivir–pleconaril combinations against EV1 infection. Conclusions: Because rupintrivir, vemurafenib, and pleconaril require lower concentrations to inhibit enterovirus replication in vitro when combined, their cocktails may have fewer side effects in vivo and, therefore, should be further explored in preclinical and clinical trials against EV1 and other enterovirus infections.
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Kanaeva, O. I. "ENTEROVIRUS INFECTION: VARIETY OF ETIOLOGICAL FACTORS AND CLINICAL MANIFESTATIONS." Russian Journal of Infection and Immunity 4, no. 1 (July 9, 2014): 27–36. http://dx.doi.org/10.15789/2220-7619-2014-1-.
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Abstract. Enteroviruses are widely distributed human infectious pathogens. In spite of infection a disease does not manifest in majority number of cases. However, in some infected persons the different kind of symptoms can be observed; from common cold signs up to aseptic (serous) meningitis and myocarditis. Severe enteroviral cases with lethal outcomes are rarely reported. Ability of enteroviruses to cause large outbreaks and even epidemic distribution is very significant for health care systems. Taking in account a high genetic diversity of enteroviruses it is possible appearance of new highly pathogenic strains in the future. In some countries including the Russian Federation the permanent surveillance for enteroviral infections is provided besides of WHO polio elimination program. The laboratory diagnostics of enterovirus infections is complicated by numerous of pathogen serotypes. Thus, classical virological methods should be supported by molecular-biological tools to sequence pathogen genome and to define phylogenetic relations between different enterovirus strains.
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van Vliet, K. E., M. Glimåker, P. Lebon, P. E. Klapper, C. E. Taylor, M. Ciardi, H. G. A. M. van der Avoort, et al. "Multicenter Evaluation of the Amplicor Enterovirus PCR Test with Cerebrospinal Fluid from Patients with Aseptic Meningitis." Journal of Clinical Microbiology 36, no. 9 (1998): 2652–57. http://dx.doi.org/10.1128/jcm.36.9.2652-2657.1998.
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The Amplicor Enterovirus PCR test was compared with viral culture for the detection of enteroviruses in cerebrospinal fluid (CSF) specimens. In a multicenter study in which nine laboratories participated, a total of 476 CSF specimens were collected from patients with suspected aseptic meningitis. Sixty-eight samples were positive by PCR (14.4%), whereas 49 samples were positive by culture (10.4%), demonstrating that the Amplicor Enterovirus PCR test was significantly more sensitive than culture (P < 0.001). After discrepancy analysis the sensitivity and specificity of the Amplicor Enterovirus PCR test obtained by using viral culture as the “gold standard” were 85.7 and 93.9%, respectively. Our results with the CSF specimens collected in different countries demonstrate that the Amplicor test is capable of detecting a large variety of enterovirus serotypes and epidemiologically unrelated isolates in CSF specimens from patients with aseptic meningitis. The Amplicor Enterovirus PCR test is a rapid assay which can be routinely performed with CSF samples and is an important improvement for the rapid diagnosis of enteroviral meningitis.
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Gregory, Jason B., R. Wayne Litaker, and Rachel T. Noble. "Rapid One-Step Quantitative Reverse Transcriptase PCR Assay with Competitive Internal Positive Control for Detection of Enteroviruses in Environmental Samples." Applied and Environmental Microbiology 72, no. 6 (June 2006): 3960–67. http://dx.doi.org/10.1128/aem.02291-05.
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ABSTRACT Human enteroviruses can serve as a more accurate indicator of human fecal contamination than conventional bacteriological fecal indicators. We describe here a quantitative reverse transcriptase PCR (qRT-PCR) assay specifically tailored to detect these viruses in environmental waters. The assay included a competitive internal positive control (CIPC) that allowed the inhibition of qRT-PCRs to be quantitatively assessed. Coamplification of the CIPC with enteroviral genetic material did not affect the sensitivity, specificity, or reproducibility of the enteroviral qRT-PCR assay. The assay is rapid (less than 5 h from sample to result), has a wide dynamic range (>3 logs), and is capable of detecting as few as 25 enteroviral genomes with an average amplification efficiency of 0.91. In samples with low or moderate inhibition, the delay in CIPC amplification was used to adjust enterovirus qRT-PCR concentrations to account for losses due to inhibition. Samples exhibiting significant inhibition were not corrected but instead diluted twofold and immediately assayed again. Using significantly inhibited samples, it was found that dilution relieved inhibition in 93% (25 of 27) of the samples. In addition, 15% (4 of 27) of these previously negative samples contained enteroviral genomes. The high-throughput format of the assay compared to conventional culture-based methods offers a fast, reliable, and specific method for detecting enteroviruses in environmental water samples. The ability of the assay to identify false negatives and provide improved quantitative assessments of enterovirus concentrations will facilitate the tracking of human fecal contamination and the assessment of potential public health risk due to enteroviruses in recreational and shellfish harvesting waters.
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McArdle, A., F. McArdle, M. J. Jackson, S. F. Page, I. Fahal, and R. H. T. Edwards. "Investigation by Polymerase Chain Reaction of Enteroviral Infection in Patients with Chronic Fatigue Syndrome." Clinical Science 90, no. 4 (April 1, 1996): 295–300. http://dx.doi.org/10.1042/cs0900295.
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1. Chronic fatigue syndrome is characterized by muscle fatigue and pain at rest, symptoms which are usually exacerbated with exercise. Although various studies have shown minor, non-specific morphological and biochemical changes in muscle of patients with chronic fatigue syndrome, no consistent defect has been identified. Some have suggested that an enteroviral infection in muscle may cause the chronic muscle fatigue seen in patients with chronic fatigue syndrome, with acute infection directly and irreversibly impairing mitochondrial function, and persistent infection depressing muscle protein synthesis and metabolism. 2. To clarify the involvement of enterovirus infection in chronic fatigue syndrome, muscle biopsies from a group of patients with chronic fatigue syndrome were examined for the presence of enteroviral RNA by reverse transcriptase-polymerase chain reaction techniques in relation to functional studies of muscle mitochondria and the muscle RNA/DNA ratio. 3. Fifty-eight percent of patients reported an uncharacterized ‘viral infection’ before the onset of their illness, but none of the muscle samples from 34 patients contained detectable amounts of enteroviral RNA. Muscle tissue had a general reduction in the RNA/DNA ratio and mitochondrial enzyme activities with no specific abnormality in the activity of enzymes encoded partially on the mitochondrial genome (cytochrome-c oxidase) or nuclear genome (citrate synthase, succinate reductase). 4. These data provide no evidence of an enteroviral infection in muscle of patients with chronic fatigue syndrome, although this does not exclude a role of enterovirus in initiating the disease process. The general reduction in RNA/DNA ratio and mitochondrial enzyme activities is consistent with a general reduction in habitual activity.
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Alimov, A. V., E. P. Igonina, I. V. Feldblyum, V. I. Chalapa, and Yu A. Zakharova. "Current status of healthcare-associated enteroviral (non-polio) infections." Russian Journal of Infection and Immunity 10, no. 3 (August 7, 2020): 486–96. http://dx.doi.org/10.15789/10.15789/2220-7619-csf-1161.
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Here we present the data on foreign research publications describing healthcare-associated enteroviral (nonpolio) infections (HAI) sought in the Worldwide Database for Nosocomial Outbreaks (Institut für Hygiene und Umweltmedizin, Universitȁtmedizincomplex “Charite”, Germany) as well as PubMed search engine (The United States National Library), covering 1936–2017 timeframe. The publications retrieved contained the data on 28 nosocomial outbreaks caused by Enterovirus A (EV-A71), В (Echoviruses 11, 17, 18, 30, 31, 33, Coxsackie viruses А9, В2, В5) and D (EV-D68). It was discovered that the majority of the nosocomial enteroviral (non-polio) outbreaks occurred in obstetric hospitals and neonatal units so that children were mainly maternally infected. In addition, a case associated with intrauterine infection was described. It was shown that outbreaks might be started by an infected child at the incubation period. Single publications reported nosocomial outbreaks in geriatric hospitals. Generally, nosocomial enteroviral (non-polio) outbreaks were characterized by polymorphic clinical picture caused by any certain pathogen serotype and within a single site of the infection. Few lethal outcomes were recorded. Enterovirus B species dominated among identified etiological agents. Violated hospital hygiene and infection control contributing to spread of infection were among those found in neonatal units: putting used diapers out on baby bed prior disposal, sharing bathtub, toys and household objects as well as poor hand hygiene in medical workers. One of the measures recommended to improve diagnostics of enteroviral (non-polio) infections was virology screening of children with suspected sepsis in case of unidentified etiology. It was established that etiological decoding of nosocomial outbreaks was impossible without applying pathogen-specific diagnostic tools, mainly nested RT-PCR and direct sequencing of followed by subsequent phylogenetic analysis.
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Young, Pampee P., Richard S. Buller, and Gregory A. Storch. "Evaluation of a Commercial DNA Enzyme Immunoassay for Detection of Enterovirus Reverse Transcription-PCR Products Amplified from Cerebrospinal Fluid Specimens." Journal of Clinical Microbiology 38, no. 11 (2000): 4260–61. http://dx.doi.org/10.1128/jcm.38.11.4260-4261.2000.
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We evaluated the DiaSorin DNA enzyme immunoassay (DEIA) kit for detection of enteroviral reverse transcription-PCR (RT-PCR) products amplified from cerebrospinal fluid. By use of an optical density of 0.05 as the absorbance cutoff, 35% of 198 specimens were PCR positive, whereas 16% were culture positive. DEIA was rapid and sensitive and can help implement enterovirus RT-PCR in clinical laboratories.
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Vergadi, Eleni, Maria Zacharioudaki, Maria Raissaki, and Emmanouil Galanakis. "Challenges in the Diagnosis of Viral Encephalitis in Children: The Case of Two Siblings." Infectious Disease Reports 14, no. 1 (February 11, 2022): 106–11. http://dx.doi.org/10.3390/idr14010014.
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Encephalitis in children may lead to adverse outcomes and long-term neurodevelopmental sequelae. The prompt identification of the causative agent is important to guide proper management in cases with encephalitis; however, the etiology often remains undetermined. The use of polymerase chain reaction (PCR) analysis in the cerebrospinal fluid (CSF) has increased the diagnostic yield in encephalitis cases; however, it may be occasionally misleading. In this article, we describe the case of a male immunocompetent child with encephalitis in which human herpesvirus-7 (HHV-7) was detected in CSF by PCR. As the detection of HHV-7 DNA in the CSF alone is insufficient to prove an etiologic association of severe encephalitis in immunocompetent children, alternative diagnoses were pursued. Enterovirus (E-11) was detected by PCR analysis of the nasopharyngeal and rectal swabs of the male patient. The final diagnosis was facilitated by the findings in his sibling, which presented concurrently with enteroviral encephalitis. Failure to detect enterovirus in the CSF by PCR does not exclude enteroviral encephalitis; screening of other samples, from other body sites, may be necessary to identify the virus, and physicians should take into consideration all evidence, including history, clinical presentation, and sick contacts’ clinical status.
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Nygårdas, Michaela, Tytti Vuorinen, Antti P. Aalto, Dennis H. Bamford, and Veijo Hukkanen. "Inhibition of coxsackievirus B3 and related enteroviruses by antiviral short interfering RNA pools produced using φ6 RNA-dependent RNA polymerase." Journal of General Virology 90, no. 10 (October 1, 2009): 2468–73. http://dx.doi.org/10.1099/vir.0.011338-0.
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Coxsackievirus B3 (CBV3) is a member of the human enterovirus B species and a common human pathogen. Even though much is known about the enteroviral life cycle, no specific drugs are available to treat enterovirus infections. RNA interference (RNAi) has evolved to be an important tool for antiviral experimental therapies and gene function studies. We describe here a novel approach for RNAi against CBVs by using a short interfering (siRNA) pool covering 3.5 kb of CBV3 genomic sequence. The RNA-dependent RNA polymerase (RdRP) of bacteriophage φ6 was used to synthesize long double-stranded RNA (dsRNA) from a cloned region (nt 3837–7399) of the CBV3 genome. The dsRNA was cleaved using Dicer, purified and introduced to cells by transfection. The siRNA pool synthesized using the φ6 RdRP (φ6–siRNAs) was considerably more effective than single-site siRNAs. The φ6–siRNA pool also inhibited replication of other enterovirus B species, such as coxsackievirus B4 and coxsackievirus A9.
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Pevear, Daniel C., Tina M. Tull, Martin E. Seipel, and James M. Groarke. "Activity of Pleconaril against Enteroviruses." Antimicrobial Agents and Chemotherapy 43, no. 9 (September 1, 1999): 2109–15. http://dx.doi.org/10.1128/aac.43.9.2109.
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ABSTRACT The activity of pleconaril in cell culture against prototypic enterovirus strains and 215 clinical isolates of the most commonly isolated enterovirus serotypes was examined. The latter viruses were isolated by the Centers for Disease Control and Prevention during the 1970s and 1980s from clinically ill subjects. Pleconaril at a concentration of ≤0.03 μM inhibited the replication of 50% of all clinical isolates tested. Ninety percent of the isolates were inhibited at a drug concentration of ≤0.18 μM. The most sensitive serotype, echovirus serotype 11, was also the most prevalent enterovirus in the United States from 1970 to 1983. Pleconaril was further tested for oral activity in three animal models of lethal enterovirus infection: coxsackievirus serotype A9 infection in suckling mice, coxsackievirus serotype A21 strain Kenny infection in weanling mice, and coxsackievirus serotype B3 strain M infection in adult mice. Treatment with pleconaril increased the survival rate in all three models for both prophylactic and therapeutic dosing regimens. Moreover, pleconaril dramatically reduced virus levels in target tissues of coxsackievirus serotype B3 strain M-infected animals. Pleconaril represents a promising new drug candidate for potential use in the treatment of human enteroviral infections.
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Galabov, Angel S., Ivanka Nikolova, Ralitsa Vassileva-Pencheva, and Adelina Stoyanova. "Antiviral Combination Approach as a Perspective to Combat Enterovirus Infections." PRILOZI 36, no. 2 (December 1, 2015): 91–99. http://dx.doi.org/10.1515/prilozi-2015-0057.
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Abstract Human enteroviruses distributed worldwide are causative agents of a broad spectrum of diseases with extremely high morbidity, including a series of severe illnesses of the central nervous system, heart, endocrine pancreas, skeleton muscles, etc., as well as the common cold contributing to the development of chronic respiratory diseases, including the chronic obstructive pulmonary disease. The above mentioned diseases along with the significantly high morbidity and mortality in children, as well as in the high-risk populations (immunodeficiencies, neonates) definitely formulate the chemotherapy as the main tool for the control of enterovirus infections. At present, clinically effective antivirals for use in the treatment of enteroviral infection do not exist, in spite of the large amount of work carried out in this field. The main reason for this is the development of drug resistance. We studied the process of development of resistance to the strongest inhibitors of enteroviruses, WIN compounds (VP1 protein hydrophobic pocket blockers), especially in the models in vivo, Coxsackievirus B (CV-B) infections in mice. We introduced the tracing of a panel of phenotypic markers (MIC50 value, plaque shape and size, stability at 50℃, pathogenicity in mice) for characterization of the drug-mutants (resistant and dependent) as a very important stage in the study of enterovirus inhibitors. Moreover, as a result of VP1 RNA sequence analysis performed on the model of disoxaril mutants of CVB1, we determined the molecular basis of the drug-resistance. The monotherapy courses were the only approach used till now. For the first time in the research for anti-enterovirus antivirals our team introduced the testing of combination effect of the selective inhibitors of enterovirus replication with different mode of action. This study resulted in the selection of a number of very effective in vitro double combinations with synergistic effect and a broad spectrum of sensitive enteroviruses. The most prospective attainment in our examinations in this field was the development of a novel scheme for the combined application of anti-enteroviral substances in coxsackievirus B1 neuroinfection in newborn mice. It consisted of a consecutive, alternating and non simultaneous administration of the substances in the combination. The triple combination - disoxaril- guanidine. HCl-oxoglaucine (DGO) showed a high effectiveness expressed in the marked reduction of the mortality rate in infected mice as compared both to the placebo group, and to the partner compounds used alone every day, and to the same combination applied simultaneously every day. The studies of the drug sensitivity of viral brain isolates from mice treated with DGO combination showed not only preserved, but even increased sensitivity to the drugs included in the combination. Obviously, the consecutive alternating administration of anti-enteroviral substances hinders the occurrence of drug-resistance in the course of the experimental enteroviral infections in mice.
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Oikarinen, Maarit, Lori Bertolet, Antonio Toniolo, Sami Oikarinen, Jutta Laiho, Alberto Pugliese, Richard Lloyd, and Heikki Hyöty. "Differential Detection of Encapsidated versus Unencapsidated Enterovirus RNA in Samples Containing Pancreatic Enzymes—Relevance for Diabetes Studies." Viruses 12, no. 7 (July 11, 2020): 747. http://dx.doi.org/10.3390/v12070747.
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Using immunohistochemistry, enterovirus capsid proteins were demonstrated in pancreatic islets of patients with type 1 diabetes. Virus proteins are mainly located in beta cells, supporting the hypothesis that enterovirus infections may contribute to the pathogenesis of type 1 diabetes. In samples of pancreatic tissue, enterovirus RNA was also detected, but in extremely small quantities and in a smaller proportion of cases compared to the enteroviral protein. Difficulties in detecting viral RNA could be due to the very small number of infected cells, the possible activity of PCR inhibitors, and the presence—during persistent infection—of the viral genome in unencapsidated forms. The aim of this study was twofold: (a) to examine if enzymes or other compounds in pancreatic tissue could affect the molecular detection of encapsidated vs. unencapsidated enterovirus forms, and (b) to compare the sensitivity of RT-PCR methods used in different laboratories. Dilutions of encapsidated and unencapsidated virus were spiked into human pancreas homogenate and analyzed by RT-PCR. Incubation of pancreatic homogenate on wet ice for 20 h did not influence the detection of encapsidated virus. In contrast, a 15-min incubation on wet ice dramatically reduced detection of unencapsidated forms of virus. PCR inhibitors could not be found in pancreatic extract. The results show that components in the pancreas homogenate may selectively affect the detection of unencapsidated forms of enterovirus. This may lead to difficulties in diagnosing persisting enterovirus infection in the pancreas of patients with type 1 diabetes.
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Ratuszny, Dominica, Kurt-Wolfram Sühs, Natalia Novoselova, Maike Kuhn, Volkhard Kaever, Thomas Skripuletz, Frank Pessler, and Martin Stangel. "Identification of Cerebrospinal Fluid Metabolites as Biomarkers for Enterovirus Meningitis." International Journal of Molecular Sciences 20, no. 2 (January 15, 2019): 337. http://dx.doi.org/10.3390/ijms20020337.
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Enteroviruses are among the most common causes of viral meningitis. Enteroviral meningitis continues to represent diagnostic challenges, as cerebrospinal fluid (CSF) cell numbers (a well validated diagnostic screening tool) may be normal in up to 15% of patients. We aimed to identify potential CSF biomarkers for enteroviral meningitis, particularly for cases with normal CSF cell count. Using targeted liquid chromatography-mass spectrometry, we determined metabolite profiles from patients with enteroviral meningitis (n = 10), and subdivided them into those with elevated (n = 5) and normal (n = 5) CSF leukocyte counts. Non-inflamed CSF samples from patients with Bell’s palsy and normal pressure hydrocephalus (n = 19) were used as controls. Analysis of 91 metabolites revealed considerable metabolic reprogramming in the meningitis samples. It identified phosphatidylcholine PC.ae.C36.3, asparagine, and glycine as an accurate (AUC, 0.92) combined classifier for enterovirus meningitis overall, and kynurenine as a perfect biomarker for enteroviral meningitis with an increased CSF cell count (AUC, 1.0). Remarkably, PC.ae.C36.3 alone emerged as a single accurate (AUC, 0.87) biomarker for enteroviral meningitis with normal cell count, and a combined classifier comprising PC.ae.C36.3, PC.ae.C36.5, and PC.ae.C38.5 achieved nearly perfect classification (AUC, 0.99). Taken together, this analysis reveals the potential of CSF metabolites as additional diagnostic tools for enteroviral meningitis, and likely other Central nervous system (CNS) infections.
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Yun, Ki Wook, Eun Hwa Choi, Doo Sung Cheon, Jina Lee, Chang Won Choi, Hee Hwang, Beyong Il Kim, Kyoung Un Park, Sung Sup Park, and Hoan Jong Lee. "Enteroviral meningitis without pleocytosis in children." Archives of Disease in Childhood 97, no. 10 (July 19, 2012): 874–78. http://dx.doi.org/10.1136/archdischild-2012-301884.
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ObjectivesThis study aims to describe the clinical characteristics of enteroviral meningitis in association with the absence of cerebrospinal fluid (CSF) pleocytosis.DesignThis was a retrospective analysis of databases of patients diagnosed with enteroviral meningitis by CSF reverse transcription-PCR testing. Presence of CSF non-pleocytosis at each age group was analysed by use of the two criteria. Clinical variables were compared with regard to the presence of CSF pleocytosis. Multiple logistic regression analysis was used to identify factors that were associated with CSF pleocytosis.SettingTwo hospitals in South Korea, between January 2008 and August 2011.Patients390 infants and children with enteroviral meningitis.InterventionsNone.Main outcome measuresProportion of enteroviral meningitis without CSF pleocytosis.ResultsAmong the 390 patients with enteroviral meningitis, 16–18% did not have CSF pleocytosis. In particular, CSF pleocytosis was not present in 68–77% of the neonates with enteroviral meningitis, demonstrating that the proportion of CSF pleocytosis decreased significantly with age (p<0.001). In multivariate models, younger age (adjusted OR 0.981; 95% CI 0.973 to 0.989), lower peripheral white blood cell count (adjusted OR 0.843; 95% CI 0.791 to 0.899), and shorter interval between onset and lumbar puncture (adjusted OR 0.527; 95% CI 0.315 to 0.882) were associated with the absence of CSF pleocytosis in enteroviral meningitis.ConclusionsThis study demonstrated high proportion of non-pleocytic enteroviral meningitis in young infants and identified several clinical factors that contributed to the absence of CSF pleocytosis. We suggest that CSF enterovirus PCR testing is likely to detect more cases of enteroviral meningitis, especially in young infants.
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Pankow, Stephanie, Nigo Masayuki, and Rodrigo Hasbun. "2652. Cytomegalovirus Meningoencephalitis: A Comparison to Other Viral CNS Infections." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S928. http://dx.doi.org/10.1093/ofid/ofz360.2330.
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Abstract Background Cytomegalovirus (CMV) is a rare cause of meningoencephalitis (ME) with clinical data limited to case reports. Methods Retrospective observational study of all viral central nervous system (CNS) infections identified in 17 hospitals in the Greater Houston area from 2000 to 2017. CMV, herpes simplex virus (HSV), varicella zoster virus (VZV), and enterovirus were all identified by a positive cerebrospinal fluid (CSF) polymerase chain reaction (PCR) and all arboviruses were identified by serology. Results A total of 361 patients with viral CNS infections were identified: CMV (n = 33), enterovirus (n = 147), herpes simplex virus (n = 83), varicella zoster virus (n = 28), and arbovirus (n = 70). CMV ME occurred more frequently in immunosuppressed patients [e.g., Acquired Immune Deficiency Syndrome (AIDS)], had more hypoglycorrhachia (59%), and had worse clinical outcomes (61%) as compared with those with HSV, enterovirus, VZV and arboviruses. Furthermore, CMV ME had more altered mental status than enterovirus and HSV and had lower CSF pleocytosis compared with HSV. Additionally, CMV ME had higher CSF protein levels than enteroviral infections and had less CSF lymphocytosis than HSV and VZV. Conclusion CMV meningoencephalitis is seen more frequently in immunosuppressed patients (e.g., AIDS), is associated with more hypoglycorrhachia and have worse clinical outcomes compared with other viral CNS pathogens. Disclosures All authors: No reported disclosures.
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Shaff, Morgan S., C. Scott Love, and Elizabeth V. Schulz. "Neonatal Enterovirus: A Case Report in a Term Infant Requiring Air Evacuation." Neonatal Network 39, no. 4 (July 1, 2020): 215–21. http://dx.doi.org/10.1891/0730-0832.39.4.215.
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Enterovirus infections in neonates have the potential to cause a cascade of devastating clinical complications that can lead to death. Because of vague maternal symptom presentations, the diagnosis may not be obvious to antepartum adult providers. Clinicians evaluating infants in the newborn nursery and following initial hospital discharge must be alert for this potential infection. Common newborn issues, such as hyperbilirubinemia and weight loss, may be early signs of a more life-threatening diagnosis. Enterovirus infections may be responsible for a continuum of critical diagnoses in the neonate. Utilization of viral panels during the initial rule-out sepsis evaluation may provide rapid diagnosis and, ultimately, earlier response times to devastating clinical symptoms. Antepartum history and presenting features of enteroviral infections warrant rapid diagnosis with viral polymerase chain reaction detection panels to potentially reduce antibiotic usage and inpatient length of stay. The purpose of this case report is to review risk factors, presentation, and management of neonatal enterovirus infections. As this infant was born in a remote setting and required air evacuation, the logistics of this transport are also discussed.
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Zuo, Jun, Steve Kye, Kevin K. Quinn, Paige Cooper, Robert Damoiseaux, and Paul Krogstad. "Discovery of Structurally Diverse Small-Molecule Compounds with Broad Antiviral Activity against Enteroviruses." Antimicrobial Agents and Chemotherapy 60, no. 3 (December 28, 2015): 1615–26. http://dx.doi.org/10.1128/aac.02646-15.
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Antiviral drugs do not currently exist for the treatment of enterovirus infections, which are often severe and potentially life-threatening. We conducted high-throughput molecular screening and identified a structurally diverse set of compounds that inhibit the replication of coxsackievirus B3, a commonly encountered enterovirus. These compounds did not interfere with the function of the viral internal ribosome entry site or with the activity of the viral proteases, but they did drastically reduce the synthesis of viral RNA and viral proteins in infected cells. Sequence analysis of compound-resistant mutants suggests that the viral 2C protein is targeted by most of these compounds. These compounds demonstrated antiviral activity against a panel of the most commonly encountered enteroviruses and thus represent potential leads for the development of broad-spectrum anti-enteroviral drugs.
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Pozo, Francisco, Inmaculada Casas, Antonio Tenorio, Gloria Trallero, and Jose M. Echevarria. "Evaluation of a Commercially Available Reverse Transcription-PCR Assay for Diagnosis of Enteroviral Infection in Archival and Prospectively Collected Cerebrospinal Fluid Specimens." Journal of Clinical Microbiology 36, no. 6 (1998): 1741–45. http://dx.doi.org/10.1128/jcm.36.6.1741-1745.1998.
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A commercially available reverse transcription (RT)-PCR method (AMPLICOR EV; Roche Diagnostic Systems, Inc., Branchburg, N.J.) was evaluated for detection of enteroviruses in cerebrospinal fluid from patients with neurological disease. This assay was compared with virus isolation in cell culture and an in-house RT-PCR method designed with a nonoverlapping region of the enteroviral genome. A panel of 200 cerebrospinal fluid specimens prospectively collected from patients with a wide variety of neurological symptoms, including 50 patients involved in three different outbreaks of acute aseptic meningitis, was assayed. A second panel of 97 archived cerebrospinal fluid specimens, stored for 2 to 5 years, from patients with aseptic meningitis associated with several enterovirus outbreaks was also studied. From the first panel, enteroviruses were detected in 13 of 50 specimens by cell culture (26%), in 43 of 50 specimens by AMPLICOR EV (86%), and in 46 of 50 specimens by the in-house assay (92%) from patients with aseptic meningitis associated with outbreak and 1 of 29, 3 of 29, and 4 of 29 specimens, respectively, from sporadic cases of aseptic meningitis. The remaining 121 cerebrospinal fluid specimens from patients with other neurological syndromes were negative by all tests. From the second panel, enteroviral RNA was detected by the AMPLICOR test (31 of 97 specimens, 32%) and the in-house assay (39 of 97 specimens, 40%). According to our results, patients with aseptic meningitis should be analyzed for enteroviral infection in cerebrospinal fluid by RT-PCR methods, and the AMPLICOR EV test is a suitable tool for performing such studies. Archival cerebrospinal fluid specimens are less suitable for evaluation of the performance of RT-PCR methods designed for enterovirus detection.
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Lukashev, A. N., L. N. Golitsina, Y. A. Vakulenko, L. V. Akhmadishina, N. I. Romanenkova, E. Yu Sapega, N. S. Morozova, N. A. Novikova, O. E. Trotsenko, and O. E. Ivanova. "CURRENT POSSIBILITIES AND POTENTIAL DEVELOPMENT OF MOLECULAR ENTEROVIRUS SURVEILLANCE. EXPERIENCE OF RUSSIAN FEDERATION." Russian Journal of Infection and Immunity 8, no. 4 (January 16, 2019): 452–64. http://dx.doi.org/10.15789/2220-7619-2018-4-452-464.
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Abstract.Enteroviruses are small RNA viruses, which are ubiquitous and commonly cause outbreaks with various clinical manifestations. In 2006, the Program on enterovirus surveillance was approved in the Russian Federation. Over the last years, molecular-biological and bioinformatics methods for enterovirus epidemiology studies have been developed both in Russia and worldwide. Currently, identification of enteroviruses is carried out by analyzing nucleotide sequence of the full-length VP1 genome region (ca. 900 nt). Routinely, it is sufficient to obtain a partial VP1 genome region sequence (ca. 300 bp) for enteroviruse verification in most cases; however, a more stringent type criterion of 80% sequence identity should be used compared to the 75% sequence identity cut-off for the complete VP1 genome region. Further sequence analysis may be performed by using Bayesian phylogenetic methods, which allow using molecular clock to trace outbreak emergence. Enteroviruses accumulate about 0.5–1% nucleotide substitutions per year. Therefore, a short genome fragment may be used to analyze virus phylodynamics at the level of international transfers and circulating virus variants. On a shorter timescale, a full-length VP1 genome region or a complete genome sequence are preferred for investigating molecular epidemiology, because a short sequence allows to reliably distinguish not more than 1–2 transmission events per year. Thus, determining enterovirus sequences for full-length VP1 genome region or full-genome sequence is preferred for examining viral outbreaks. It is increasingly apparent that analyzing available enterovirus nucleotide sequences reveals limitations related to uneven surveillance efficacy in various countries and short length of genome fragment measured in routine control. As a result, a proper global-scale analysis of enterovirus molecular epidemiology remains problematic. Over the last 20 years, the number of available enterovirus nucleotide sequences increased by hundred times, but understanding emergence of enterovirus infection outbreaks remains limited. Further development of enterovirus surveillance would require new methods for sewage monitoring, affordable high-throughput sequencing and harmonization of global surveillance systems.
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Orzechowska, Magda, Elżbieta Krajewska-Kułak, and Mateusz Cybulski. "An outbreak of aseptic meningitis in Podlaskie Voivodeship in 2014." Aktualności Neurologiczne 16, no. 4 (December 30, 2016): 212–17. http://dx.doi.org/10.15557/an.2016.0028.
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Enteroviruses cause common infections with various clinical course and forms, such as hand-foot-and-mouth disease (Boston exanthem disease), herpangina, myocarditis and pericarditis, widespread myositis (epidemic pleurodynia, Bornholm disease), or aseptic inflammation of the nervous system, among children and adolescents. An increase in aseptic meningitis cases of enteroviral aetiology, including the E30 virus, was occasionally observed in various European countries. In 2014, an outbreak of aseptic meningitis was reported in Podlaskie Voivodeship. A total of 640 cases were reported between June 1 and November 30, 2014, of which 228 had confirmed enteroviral aetiology. Summer and autumn seasons favour the incidence of viral infections of the central nervous system. Symptomatic infections are more common in males than females. Infections with enterovirus show the tendency to form endemic regions.
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Lindfors, Katri, Jake Lin, Hye-Seung Lee, Heikki Hyöty, Matti Nykter, Kalle Kurppa, Edwin Liu, et al. "Metagenomics of the faecal virome indicate a cumulative effect of enterovirus and gluten amount on the risk of coeliac disease autoimmunity in genetically at risk children: the TEDDY study." Gut 69, no. 8 (November 19, 2019): 1416–22. http://dx.doi.org/10.1136/gutjnl-2019-319809.
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ObjectiveHigher gluten intake, frequent gastrointestinal infections and adenovirus, enterovirus, rotavirus and reovirus have been proposed as environmental triggers for coeliac disease. However, it is not known whether an interaction exists between the ingested gluten amount and viral exposures in the development of coeliac disease. This study investigated whether distinct viral exposures alone or together with gluten increase the risk of coeliac disease autoimmunity (CDA) in genetically predisposed children.DesignThe Environmental Determinants of Diabetes in the Young study prospectively followed children carrying the HLA risk haplotypes DQ2 and/or DQ8 and constructed a nested case–control design. From this design, 83 CDA case–control pairs were identified. Median age of CDA was 31 months. Stool samples collected monthly up to the age of 2 years were analysed for virome composition by Illumina next-generation sequencing followed by comprehensive computational virus profiling.ResultsThe cumulative number of stool enteroviral exposures between 1 and 2 years of age was associated with an increased risk for CDA. In addition, there was a significant interaction between cumulative stool enteroviral exposures and gluten consumption. The risk conferred by stool enteroviruses was increased in cases reporting higher gluten intake.ConclusionsFrequent exposure to enterovirus between 1 and 2 years of age was associated with increased risk of CDA. The increased risk conferred by the interaction between enteroviruses and higher gluten intake indicate a cumulative effect of these factors in the development of CDA.
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Sham, L., R. Yeung, S. Dell, A. Bitnun, J. Johnstone, and E. Yeh. "P.029 Case report: pediatric enterovirus encephalitis - a rare complication of rituximab therapy." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 45, s2 (June 2018): S23. http://dx.doi.org/10.1017/cjn.2018.131.
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Background: Opportunistic infection should be considered when seeing neurological complications in the setting of immunosuppression. Accumulating evidence that enteroviral meningoencephalitis can occur after rituximab administration exists but differentiating it from non-infectious conditions can be challenging. Methods: Case report Results: We describe a 4 year-old-boy with a history of pulmonary capillaritis, treated with immunosuppressive therapy -including steroids, rituximab, and azathioprine. He developed mutism and ataxia after 18 months on rituximab. MRI Brain/Spine revealed extensive T2/FLAIR hyperintensities in the deep subcortical white matter, temporal lobes, globus pallidi, thalami, brainstem, and cerebellum; and swelling of the dorsal cervical cord, showing primarily grey matter involvement. IgG levels had a decreasing trend over the course of Rituximab. CSF, and subsequent brain biopsy, were both positive for enterovirus RNA by RT-PCR. He was thought to have enterovirus encephalitis secondary to rituximab therapy, and was treated with IVIG and fluoxetine. Conclusions: One should consider chronic opportunistic CNS infections in children treated with immunosuppressive therapy, and to consider chronic enterovirus infection when B-cell suppression has occurred. As rituximab is being increasingly used in the pediatric population, and is generally thought to be safe, attention should be paid to any child with chronic neurological signs, particularly younger children who may be at higher risk for chronic enterovirus infection.
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Hadziyannis, Emilia, Nancy Cornish, Colleen Starkey, Gary W. Procop, and Belinda Yen-Lieberman. "Amplicor Enterovirus Polymerase Chain Reaction in Patients With Aseptic Meningitis." Archives of Pathology & Laboratory Medicine 123, no. 10 (October 1, 1999): 882–84. http://dx.doi.org/10.5858/1999-123-0882-aepcri.
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Abstract Objective.—To evaluate the sensitivity and specificity of reverse-transcription polymerase chain reaction (RT-PCR) and routine cell culture for the detection of enterovirus in cerebrospinal fluid. Methods.—Thirty-eight cerebrospinal fluid specimens were included. Cell culture was inoculated immediately and incubated for 14 days. An aliquot was kept frozen for Amplicor RT-PCR. Chart review was performed to determine the validity of the results. Results.—Nine of 38 specimens were positive for enterovirus by culture, and 14 were positive by RT-PCR. There were 7 discrepancies between the 2 methods. Six specimens were positive by RT-PCR and negative by the culture method. The 1 culture-positive but RT-PCR–-negative specimen was determined to contain PCR inhibitors. All discrepant results were confirmed as true positives by chart review. Patients whose cerebrospinal fluid was negative by both methods had a final diagnosis other than enterovirus infection. Conclusion.—Amplicor PCR is more sensitive than cell culture (93.3% vs 60%) and is very specific. With the incorporation of appropriate controls for the detection of amplification inhibitors, RT-PCR could be a valuable tool in the diagnosis of enteroviral meningitis.
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Kokoreva, S. P., N. V. Kazartseva, and V. B. Kotlova. "The evolution of clinical and laboratory features enteroviral meningitis in children." CHILDREN INFECTIONS 18, no. 4 (December 6, 2019): 43–48. http://dx.doi.org/10.22627/2072-8107-2019-18-4-43-48.
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In recent years, enterovirus infection (EVI) retains its cyclical nature with an increase in the incidence rate in the Russian Federation in 2000, 2006, 2009, 2013 and 2017. Observation of 41 patients with laboratory-confirmed enteroviral meningitis (EVM) in 2000, 54 children in 2013, and 56 patients in 2018 revealed the clinical and laboratory features of this clinical form of the disease, mainly concerning changes in hemo- and liquorogram parameters, which allowed to trace the evolutionary changes during this infection in children.
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Cameron Smail, Ruaridh, John H. O’Neill, and David Andresen. "Brainstem encephalitis caused by Coxsackie A16 virus in a rituximab-immunosuppressed patient." BMJ Case Reports 12, no. 8 (August 2019): e230177. http://dx.doi.org/10.1136/bcr-2019-230177.
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Rituximab and other B cell depleting agents are increasingly used for haematological, immunological and neurological diseases. In a small minority, immunosuppression leads to increased virulence of normally mild infections. Brainstem encephalitis has been described occurring after infection from enteroviruses, more commonly in the paediatric population, but also in immunosuppressed adults. In this paper, we describe an enteroviral brainstem encephalitis in a rituximab-immunosuppressed patient. The enterovirus identified was Coxsackie A16, which has never yet been reported to cause brainstem encephalitis in an adult.
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Lin, Chien-Yu, Shih-Yu Huang, Chuen-Bin Jiang, Chun-Chih Peng, Hsin Chi, and Nan-Chang Chiu. "Enteroviral Rhombencephalitis with Abducens Nerve Palsy and Cardio-Pulmonary Failure in a 2-Year-Old Boy." Children 9, no. 5 (April 29, 2022): 643. http://dx.doi.org/10.3390/children9050643.
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Enterovirus infection is endemic in many areas, especially in Southeast Asia. Enterovirus infection with severe complications (EVSC) is life-threatening, and timely diagnosis and management are crucial for successful management. Here, we report on a 2-year-old boy with hand, foot, and mouth disease. Myoclonic jerks developed and left abducens nerve palsy followed. Brain magnetic resonance imaging (MRI) showed rhombencephalitis. Pulmonary edema and cardiopulmonary failure developed, and intravenous immunoglobulin and extracorporeal membrane oxygenation were administered. He had a tracheostomy with home ventilator use after 64 days of hospitalization. At a 5-year follow-up, his neurodevelopment was normal with complete recovery from the abducens nerve palsy. The progress of EVSC may be rapid and fulminant, and timely diagnosis is critical for patient prognosis and outcomes. The presence of abducens nerve palsy is an indicator of enteroviral rhombencephalitis, and immediate and appropriate management is suggested.
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CHANSAENROJ, J., S. VONGPUNSAWAD, J. PUENPA, A. THEAMBOONLERS, V. VUTHITANACHOT, P. CHATTAKUL, D. AREECHOKCHAI, and Y. POOVORAWAN. "Epidemic outbreak of acute haemorrhagic conjunctivitis caused by coxsackievirus A24 in Thailand, 2014." Epidemiology and Infection 143, no. 14 (March 31, 2015): 3087–93. http://dx.doi.org/10.1017/s0950268815000643.
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SUMMARYAcute haemorrhagic conjunctivitis outbreaks are often attributed to viral infection. In 2014, an unprecedented nationwide outbreak of infectious conjunctivitis occurred in Thailand, which affected >300 000 individuals over 3 months. To identify and characterize the virus responsible for the epidemic, eye swab specimens from 119 patients were randomly collected from five different provinces. Conserved regions in the enteroviral 5′-UTR and adenovirus hexon gene were analysed. Enterovirus was identified in 71·43% (85/119) of the samples, while no adenovirus was detected. From enterovirus-positive samples, the coxsackievirus A24 variant (70·59%, 84/119) and echovirus (0·84%, 1/119) were identified. Additional sequencing of full-length VP1 and 3C genes and subsequent phylogenetic analysis revealed that these clinical isolates form a new lineage cluster related to genotype IV-C5. In summary, the coxsackievirus A24 variant was identified as an aetiological agent for the recent acute haemorrhagic conjunctivitis outbreak in Thailand.
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Min, Nyo, Yasmin Hui Binn Ong, Alvin X. Han, Si Xian Ho, Emmerie Wong Phaik Yen, Kenneth Hon Kim Ban, Sebastian Maurer-Stroh, Chia Yin Chong, and Justin Jang Hann Chu. "An epidemiological surveillance of hand foot and mouth disease in paediatric patients and in community: A Singapore retrospective cohort study, 2013–2018." PLOS Neglected Tropical Diseases 15, no. 2 (February 10, 2021): e0008885. http://dx.doi.org/10.1371/journal.pntd.0008885.
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Background While hand, foot and mouth disease (HFMD) is primarily self-resolving—soaring incidence rate of symptomatic HFMD effectuates economic burden in the Asia-Pacific region. Singapore has seen a conspicuous rise in the number of HFMD cases from 2010s. Here, we aims to identify the serology and genotypes responsible for such outbreaks in hospitals and childcare facilities. Methods We studied symptomatic paediatric HFMD cases from 2013 to 2018 in Singapore. Surveillance for subclinical enterovirus infections was also performed in childcares at the same time period. Results Genotyping 101 symptomatic HFMD samples revealed CV-A6 as the major etiological agent for recent outbreaks. We detected infections with CV-A6 (41.0%), EV-A71 (7%), CV-A16 (3.0%), coxsackievirus A2, CV-A2 (1.0%) and coxsackievirus A10, CV-A10 (1.0%). Phylogenetic analysis of local CV-A6 strains revealed a high level of heterogeneity compared against others worldwide, dissimilar to other HFMD causative enteroviruses for which the dominant strains and genotypes are highly region specific. We detected sub-clinical enterovirus infections in childcare centres; 17.1% (n = 245) tested positive for enterovirus in saliva, without HFMD indicative symptoms at the point of sample collection. Conclusions CV-A6 remained as the dominant HFMD causative strain in Singapore. Silent subclinical enteroviral infections were detected and warrant further investigations.
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Laajala, Mira, Minna M. Hankaniemi, Juha A. E. Määttä, Vesa P. Hytönen, Olli H. Laitinen, and Varpu Marjomäki. "Host Cell Calpains Can Cleave Structural Proteins from the Enterovirus Polyprotein." Viruses 11, no. 12 (November 28, 2019): 1106. http://dx.doi.org/10.3390/v11121106.
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Enteroviruses are small RNA viruses that cause diseases with various symptoms ranging from mild to severe. Enterovirus proteins are translated as a single polyprotein, which is cleaved by viral proteases to release capsid and nonstructural proteins. Here, we show that also cellular calpains have a potential role in the processing of the enteroviral polyprotein. Using purified calpains 1 and 2 in an in vitro assay, we show that addition of calpains leads to an increase in the release of VP1 and VP3 capsid proteins from P1 of enterovirus B species, detected by western blotting. This was prevented with a calpain inhibitor and was dependent on optimal calcium concentration, especially for calpain 2. In addition, calpain cleavage at the VP3-VP1 interface was supported by a competition assay using a peptide containing the VP3-VP1 cleavage site. Moreover, a mass spectrometry analysis showed that calpains can cleave this same peptide at the VP3-VP1 interface, the cutting site being two amino acids aside from 3C’s cutting site. Furthermore, we show that calpains cannot cleave between P1 and 2A. In conclusion, we show that cellular proteases, calpains, can cleave structural proteins from enterovirus polyprotein in vitro. Whether they assist polyprotein processing in infected cells remains to be shown.
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Richter, Jan, Dana Koptides, Christina Tryfonos, and Christina Christodoulou. "Molecular typing of enteroviruses associated with viral meningitis in Cyprus, 2000–2002." Journal of Medical Microbiology 55, no. 8 (August 1, 2006): 1035–41. http://dx.doi.org/10.1099/jmm.0.46447-0.
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Human enteroviruses are responsible for a wide spectrum of clinical diseases affecting many different organ systems. Although infection is usually asymptomatic, infections of the central nervous system manifested as meningitis or encephalitis can pose a serious public health problem, especially during outbreaks. In this study, samples from 218 patients diagnosed with enteroviral meningitis between January 2000 and December 2002 were analysed in order to assess the epidemiology of human enteroviruses as a cause of viral meningitis in Cyprus. A new typing strategy, based on partial sequencing of the 5′ non-coding region (5′NCR), prediction of type, and selection of type-specific primers for sensitive VP1 PCR amplification, was developed. As clustering in the 5′NCR was concordant with clustering in the VP1 region, quick and reliable typing by VP1 sequencing was achieved without virus isolation in cell culture. The most frequent enterovirus serotypes identified were Human echovirus 30 (55.5 %), Human echovirus 13 (15.1 %), Human echovirus 6 (13.8 %) and Human echovirus 9 (8.3 %). Human coxsackieviruses B2, B1 and B5, Human echovirus 4, Human enterovirus 71 and Human coxsackievirus A6 represented rather rare serotypes. This is the first molecular epidemiological study of enterovirus meningitis in Cyprus. Serotype distribution corresponded basically with observations in other European countries, suggesting the spread of enteroviruses by tourism.
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Park, Kwi Sung, Young Jin Choi, and Joon Soo Park. "Enterovirus infection in Korean children and anti-enteroviral potential candidate agents." Korean Journal of Pediatrics 55, no. 10 (2012): 359. http://dx.doi.org/10.3345/kjp.2012.55.10.359.
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Yang, Xiaoyao, Chiara Aloise, Arno L. W. van Vliet, Marleen Zwaagstra, Heyrhyoung Lyoo, Anchun Cheng, and Frank J. M. van Kuppeveld. "Proteolytic Activities of Enterovirus 2A Do Not Depend on Its Interaction with SETD3." Viruses 14, no. 7 (June 22, 2022): 1360. http://dx.doi.org/10.3390/v14071360.
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Enterovirus 2Apro is a protease that proteolytically processes the viral polyprotein and cleaves several host proteins to antagonize host responses during enteroviral infection. Recently, the host protein actin histidine methyltransferase SET domain containing 3 (SETD3) was identified to interact with 2Apro and to be essential for virus replication. The role of SETD3 and its interaction with 2Apro remain unclear. In this study, we investigated the potential involvement of SETD3 in several functions of 2Apro. For this, we introduced the 2Apro from coxsackievirus B3 (CVB3) in a mutant of encephalomyocarditis virus (EMCV) containing an inactivated Leader protein (EMCV-Lzn) that is unable to shut down host mRNA translation, to trigger nucleocytoplasmic transport disorder (NCTD), and to suppress stress granule (SG) formation and type I interferon (IFN) induction. Both in wt HeLa cells and in HeLa SETD3 knockout (SETD3KO) cells, the virus containing active 2Apro (EMCV-2Apro) efficiently cleaved eukaryotic translation initiation factor 4 gamma (eIF4G) to shut off host mRNA translation, cleaved nucleoporins to trigger NCTD, and actively suppressed SG formation and IFN gene transcription, arguing against a role of SETD3 in these 2Apro-mediated functions. Surprisingly, we observed that the catalytic activity of enteroviral 2A is not crucial for triggering NCTD, as a virus containing an inactive 2Apro (EMCV-2Am) induced NCTD in both wt and SETD3KO cells, albeit delayed, challenging the idea that the NCTD critically depends on nucleoporin cleavage by this protease. Taken together, our results do not support a role of SETD3 in the proteolytic activities of enterovirus 2Apro.
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Holland, Diane T., Jill Senne, C. R. Peter, Connie Urmeneta, and J. D. Connor. "Differentiation and Characterization of Enteroviruses by Computer-Assisted Viral Protein Fingerprinting." Journal of Clinical Microbiology 36, no. 6 (1998): 1588–94. http://dx.doi.org/10.1128/jcm.36.6.1588-1594.1998.
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We have developed and standardized a computerized method for the typing and characterization of enteroviruses with radiolabeled viral protein fingerprints. Enteroviral proteins were radiolabeled with [35S]methionine during growth in cell culture and were then separated by polyacrylamide gel electrophoresis. The dried gel was scanned, and from the resulting computer image (which resembled an autoradiogram) protein patterns were computer extracted and stored in a database. The enterovirus database contained community and prototype strains belonging to 20 different enteroviral serotypes. Each serotype has a discrete protein pattern, and the most important pattern differences for determining each type are in the region of the viral capsid proteins VP1, VP2, and VP3. When the database was challenged with 148 clinical enterovirus strains, 144 (97%) were correctly identified by using the correlation coefficient as a quantitative measure of relatedness between two patterns. This method can identify a type in a single test and represents a practical alternative to virus neutralization because it is less expensive, is much faster (3 rather than 10 days), and does not rely on any virus-specific reagents. The results also show that most of the strains currently isolated from the community have protein patterns different from those of their older prototype strains. Viral protein fingerprinting is an evolving, dynamic system for the typing and characterization of enteroviruses. The method is appropriate for use in clinical virology and reference laboratories for the typing of enteroviruses, for the study of the epidemiology of enteroviruses, and for surveillance of enteroviruses.
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Cheng, Mei-Ling, Chien-Hsiang Wu, Kun-Yi Chien, Chien-Hsueh Lai, Guan-Jie Li, Yuan-Yu Liu, Gigin Lin, and Hung-Yao Ho. "Enteroviral 2B Interacts with VDAC3 to Regulate Reactive Oxygen Species Generation That Is Essential to Viral Replication." Viruses 14, no. 8 (August 4, 2022): 1717. http://dx.doi.org/10.3390/v14081717.
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Enterovirus (EV) 71 caused episodes of outbreaks in China and Southeast Asia during the last few decades. We have previously reported that EV71 induces reactive oxygen species (ROS). However, the underlying mechanism remains elusive. Co-immunoprecipitation-proteomic analysis revealed that enteroviral 2B protein interacted with mitochondrial voltage-dependent anion channel 3 (VDAC3). Knockdown (KD) of VDAC3 expression specifically inhibited enteroviral replication. Single-round viral replication was also inhibited in KD cells, suggesting that VDAC3 plays an essential role in replication. Consistent with this, VDAC3 gene KD significantly reduced the EV71-induced mitochondrial ROS generation. Exogenous 2B expression could induce the mitochondrial ROS generation that was significantly reduced in VDAC3-KD cells or in the Mito-TEMPO-treated cells. Moreover, VDAC3 appears to be necessary for regulation of antioxidant metabolism. VDAC3 gene KD led to the enhancement of such pathways as hypotaurine/taurine synthesis in the infected cells. Taken together, these findings suggest that 2B and VDAC3 interact to enhance mitochondrial ROS generation, which promotes viral replication.
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Hughes, M. S., P. V. Coyle, and J. H. Connolly. "Enteroviruses in recreational waters of Northern Ireland." Epidemiology and Infection 108, no. 3 (June 1992): 529–36. http://dx.doi.org/10.1017/s0950268800050020.
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SUMMARYVirus surveillance of Northern Ireland recreational waters, between April 1986 and May 1989 demonstrated widespread enteroviral contamination of coastal and inland waters. In 1986, enteroviruses were detected in 4 of 46 (8·7%) water samples, collected from 6 coastal bathing waters. In 1987, 49 of 107 (45·8%) samples, from 16 coastal bathing waters, yielded enteroviruses; 33 of the enterovirus positive samples passed one or both of the coliform standards outlined by the European Economic Community (EEC) bathing water directive (76/160/EEC). Enteroviruses were also detected in 33 of 39 (84·6%) samples tested from 3 inland recreational waters.
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Joshi, Yadav, Jong-Hun Kim, Ho Kim, and Hae-Kwan Cheong. "Impact of Drinking Water Quality on the Development of Enteroviral Diseases in Korea." International Journal of Environmental Research and Public Health 15, no. 11 (November 14, 2018): 2551. http://dx.doi.org/10.3390/ijerph15112551.
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Enterovirus diseases are fecal-orally transmitted, and its transmission may be closely related with the drinking water quality and other environmental factors. This study aimed to assess the association between environmental factors including drinking water quality and the incidence of enteroviral diseases in metropolitan provinces of Korea. Using monthly number of hand-foot-mouth disease (HFMD), aseptic meningitis (AM) and acute hemorrhage conjunctivitis (AHC) cases, generalized linear Poisson model was applied to estimate the effects of environmental factors on the monthly cases. An increase of mean temperature was associated with an increase of enteroviral diseases at 0–2 months lag, while an increase of turbidity was associated with increase in HFMD at 1 month lag and a decrease in AHC. An increase of residual chlorine in municipal drinking water was associated with a decrease in HFMD and AHC 2 and 3 months later. An increase of pH was associated with a maximum increase in AM 3 months later. The meta-analysis revealed the effects of the provincial and pooled variation in percent change of risks of environmental factors on HFMD, AM, and AHC cases at specific selected lags. This study suggests that the drinking water quality is one of the major determinants on enteroviral diseases.
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Russo, Denise Hage, Adriana Luchs, Bráulio Caetano Machado, Rita de Cássia Carmona, and Maria do Carmo Sampaio Timenetsky. "Echovirus 4 associated to hand, foot and mouth disease." Revista do Instituto de Medicina Tropical de São Paulo 48, no. 4 (August 2006): 197–99. http://dx.doi.org/10.1590/s0036-46652006000400004.
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Hand, foot and mouth disease (HFMD) is a contagious enteroviral infection occurring primarily in children and characterized by vesicular palmoplantar eruptions and erosive stomatitis. Echovirus 4 (EV-4) has been commonly associated with aseptic meningitis. The association of HFMD with EV-4 has not been reported previously. Two samples of a 14-month child who presented mild fever, sores in the mouth, rash with blisters on the palm of hands and soles of feet were sent to Enteric Viruses Laboratory of Adolfo Lutz Institute. Clinical samples were inoculated in three different cell lines, and those which presented cytopathic effect (CPE), were submitted to Indirect Immunofluorescence Assay (IFA) and "one step" RT-PCR. Agarose gel electrophoresis from RT-PCR product, showed a product with 437 bp, which is characteristic of Enterovirus group. Echovirus 4 was identified by IFA. Although HFMD is a viral infection associated mainly with Enterovirus 71 (HEV-71) and Coxsackievirus A16 (CV-A16), our results demonstrate a diversity of serotype related to HFMD and stress the importance of epidemiological surveillance to this disease and its complications.
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Saarinen, Niila V. V., Virginia M. Stone, Minna M. Hankaniemi, Magdalena A. Mazur, Tytti Vuorinen, Malin Flodström-Tullberg, Heikki Hyöty, Vesa P. Hytönen, and Olli H. Laitinen. "Antibody Responses against Enterovirus Proteases are Potential Markers for an Acute Infection." Viruses 12, no. 1 (January 9, 2020): 78. http://dx.doi.org/10.3390/v12010078.
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Background: Enteroviruses are a group of common non-enveloped RNA viruses that cause symptoms ranging from mild respiratory infections to paralysis. Due to the abundance of enterovirus infections it is hard to distinguish between on-going and previous infections using immunological assays unless the IgM fraction is studied. Methods: In this study we show using Indirect ELISA and capture IgM ELISA that an IgG antibody response against the nonstructural enteroviral proteins 2A and 3C can be used to distinguish between IgM positive (n = 22) and IgM negative (n = 20) human patients with 83% accuracy and a diagnostic odds ratio of 30. Using a mouse model, we establish that the antibody response to the proteases is short-lived compared to the antibody response to the structural proteins in. As such, the protease antibody response serves as a potential marker for an acute infection. Conclusions: Antibody responses against enterovirus proteases are shorter-lived than against structural proteins and can differentiate between IgM positive and negative patients, and therefore they are a potential marker for acute infections.
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Van Doornum, G. J. J., and J. C. De Jong. "Rapid Shell Vial Culture Technique for Detection of Enteroviruses and Adenoviruses in Fecal Specimens: Comparison with Conventional Virus Isolation Method." Journal of Clinical Microbiology 36, no. 10 (1998): 2865–68. http://dx.doi.org/10.1128/jcm.36.10.2865-2868.1998.
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Detection of enteroviruses and adenoviruses mainly in fecal specimens by rapid culture with inoculation onto cell monolayers in flat-bottom tubes by centrifugation and immunofluorescence staining with genus-specific monoclonal antibodies was compared with that by the conventional virus isolation procedure. For both conventional culture and shell vial culture human lung fibroblast cells and tertiary monkey kidney cells were used. For enterovirus detection, 979 clinical specimens (916 stool specimens, 56 cerebrospinal fluid specimens, and 7 nasopharyngeal swabs) were used. Conventional culture detected 74 enterovirus isolates. A cytopathic effect compatible with the presence of an enterovirus after 3 days of incubation occurred in 25 of the 74 (34%) specimens that eventually became positive. The detection rate for enteroviruses by rapid cell culture after 2 to 3 days of incubation was 42 of 74 (57%). The genus-specific enterovirus monoclonal antibody did not react with strains of echovirus types 22 and 23 or enterovirus type 71. Rapid cell culture for the detection of adenoviruses was performed with 567 clinical specimens (536 stool specimens, 25 cerebrospinal fluid specimens, and 6 miscellaneous specimens), in which 42 adenoviruses were found by conventional culture. Nine of the 42 (21%) adenovirus isolates were detected by conventional culture within 3 days after inoculation, whereas 21 (50%) were found by rapid cell culture within 2 to 3 days. Only two of the nine specimens found to be positive for the enteric adenovirus type 41 by conventional culture as well by a type-specific enzyme-linked immunosorbent assay (ELISA) tested positive by rapid cell culture. In conclusion, the rapid shell vial assay allows the early detection and identification of enteroviruses and adenoviruses in clinical specimens but is markedly less sensitive than the conventional isolation procedure according to the eventual results of the conventional isolation procedure. Conventional cell culture remains a prerequisite for serotyping of enteroviral isolates. On the basis of the results for adenovirus type 41, the rapid detection of adenoviruses was not considered to be useful for the detection of clinically relevant adenoviruses in fecal samples.
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Merkle, Ingrid, Mark J. M. van Ooij, Frank J. M. van Kuppeveld, Dirk H. R. F. Glaudemans, Jochem M. D. Galama, Andreas Henke, Roland Zell, and Willem J. G. Melchers. "Biological Significance of a Human Enterovirus B-Specific RNA Element in the 3′ Nontranslated Region." Journal of Virology 76, no. 19 (October 1, 2002): 9900–9909. http://dx.doi.org/10.1128/jvi.76.19.9900-9909.2002.
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ABSTRACT The secondary structures predicted for the enteroviral 3′ nontranslated region (3′NTR) all seem to indicate a conformation consisting of two (X and Y) hairpin structures. The higher-order RNA structure of the 3′NTR appears to exist as an intramolecular kissing interaction between the loops of these two hairpin structures. The enterovirus B-like subgroup possesses an additional stem-loop structure, domain Z, which is not present in the poliovirus-like enteroviruses. It has been suggested that the Z domain originated from a burst of short sequence repetitions (E. V. Pilipenko, S. V. Maslova, A. N. Sinyakov, and V. I. Agol, Nucleic Acids Res. 20:1739-1745, 1992). However, no functional features have yet been ascribed to this enterovirus B-like-specific RNA element in the 3′NTR. In this study, we tested the functional characteristics and biological significance of domain Z. A mutant of the cardiovirulent coxsackievirus group B3 strain Nancy which completely lacked the Z domain and which therefore acquired enterovirus C-like secondary structures exhibited a wild-type growth phenotype, as determined by single-cycle growth analysis with BGM cells. This result proves that the Z domain is virtually dispensable for viral growth in tissue cultures. Partial distortion of the Z domain structure resulted in a disabled virus with reduced growth kinetics, probably due to alternative conformations of the overall structure of the domain. Infection of mice showed that the recombinant coxsackievirus group B3 mutant which completely lacked the Z domain was less virulent. Pancreatic tissues from mice infected with wild-type virus and recombinant virus were equally affected. However, the heart tissue from mice infected with the recombinant virus showed only slight signs of myocarditis. These results suggest that the enterovirus B-like-specific Z domain plays a role in coxsackievirus-induced pathogenesis.
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Ramalho, Emanuelle, Ivanildo Sousa, Fernanda Burlandy, Eliane Costa, Amanda Dias, Roseane Serrano, Maria Oliveira, et al. "Identification and Phylogenetic Characterization of Human Enteroviruses Isolated from Cases of Aseptic Meningitis in Brazil, 2013–2017." Viruses 11, no. 8 (July 29, 2019): 690. http://dx.doi.org/10.3390/v11080690.
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Aseptic meningitis is a common viral infection associated with human enteroviruses. The aim of the present study was to identify and characterize the enteroviruses associated with outbreaks and sporadic cases of aseptic meningitis that occurred in different regions of Brazil between 2013 and 2017. Cerebrospinal fluids obtained from patients admitted to public health facilities were analyzed. A total of 303 patients were positive for Human Enteroviruses (EV) by cell culture isolation with a median isolation rate throughout the year of 12%. We were able to identify enterovirus serotypes in 295 clinical specimens. Nineteen different serotypes were identified; the large majority corresponded to HEV-B species. Echovirus 30 (E-30) and Echovirus 6 (E-6) were the most prevalent genotypes (66.8%). Sequence analysis suggested that circulating E-30 was closely related to E-30 from other American countries; while E-6 was derived from Europe. Most of the patients consisted of children ≤ 15 years old. The temporal distribution of all aseptic meningitis and EV-positive cases showed an obvious seasonal pattern during autumn. Our results have provided valuable information about the enteroviral etiology of the aseptic meningitis cases in Brazil pointing to the importance of enterovirus surveillance in neurological diseases.
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Weinzierl, Andreas O., Despina Rudolf, Dominik Maurer, Dorothee Wernet, Hans-Georg Rammensee, Stefan Stevanović, and Karin Klingel. "Identification of HLA-A*01- and HLA-A*02-restricted CD8+ T-cell epitopes shared among group B enteroviruses." Journal of General Virology 89, no. 9 (September 1, 2008): 2090–97. http://dx.doi.org/10.1099/vir.0.2008/000711-0.
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Acute enteroviral infections ranging from meningitis, pancreatitis to myocarditis are common and normally well controlled by the host immune system comprising virus-specific CD8+ cytotoxic T lymphocytes (CTL). However, in some patients enteroviruses and especially coxsackieviruses of group B are capable of inducing severe chronic forms of diseases such as chronic myocarditis. Currently, it is not known whether divergences in the CTL-related immune response may contribute to the different outcome and course of enterovirus myocarditis. A pre-requisite for the study of CTL reactions in patients with acute and chronic myocarditis is the identification of CTL epitopes. In order to define dominant enterovirus CTL epitopes, we have screened, by using gamma interferon (IFN-γ) ELISPOT, 62 HLA-A*01- and 59 HLA-A*02-positive healthy blood donors for pre-existing CTL reactions against 12 HLA-A*01 and 20 HLA-A*02 predicted CTL epitopes derived from coxsackieviruses of group B. Positive CTL reactions were verified by FACS analysis in a combined major histocompatibility complex-tetramer IFN-γ staining. A total of 14.8 % of all donors reacted against one of the three identified epitopes MLDGHLIAFDY, YGDDVIASY or GIIYIIYKL. The HLA-A*02-restricted epitope ILMNDQEVGV was recognized by 25 % of all tested blood donors. For this peptide, we could demonstrate specific granzyme B secretion, a strong cytolytic potential and endogenous processing. All four epitopes were homologous in 36–92 % of group B enteroviruses, providing a strong basis for monitoring the divergence of T-cell-based immune responses in enterovirus-induced acute and chronic diseases.
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Rasti, Mojtaba, Manoochehr Makvandi, Niloofar Neisi, Azarakhsh Azaran, Nasrin Rastegarvand, Davod Khalafkhany, Emad Jahangirnezhad, et al. "Three cases of mumps virus and enterovirus coinfection in children with enteroviral meningitis." Medicine 95, no. 49 (December 2016): e5610. http://dx.doi.org/10.1097/md.0000000000005610.
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Şensoy, Gülnar, Kutay Sel, Ethem Özkaya, Bahar Çuhaci Çakir, Sadi Vidinlisan, and Levent Doganci. "Enteroviral meningitis in children in Turkey." Open Medicine 4, no. 2 (June 1, 2009): 253–58. http://dx.doi.org/10.2478/s11536-008-0055-5.
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AbstractIn the indexed medical literature, there have been a very limited number of studies to investigate the epidemiologic and clinical features of enteroviral meningitis in Turkey. The aim of the present retrospective study is to update the actual situation to recognize the spectrum and magnitude of this important clinical entity. Between June 1999 and December 2004, 612 cases of aseptic meningitis were followed up at our hospital. Enteroviral meningitis was defined by isolation of enteroviruses from cerebrospinal fluid (CSF) and/or stool samples. Mumps virus was detected in 310 cases (50.7%) and enteroviruses were the etiologic agents in 104 (17%) of the patients with aseptic meningitis. Most of the enteroviral meningitis cases (36 cases, 34.6%) were diagnosed in August and 70 (67.3%) of them were male. The mean age was 5.6 ± 3.4 years. The most common initial symptoms were fever (81.7%), vomiting (77.9%) and headache (57.7%). In the physical examination, 46.2% of the cases had neck stiffness and 38.5% had pharyngitis. Echovirus 30 was the most frequently (38 cases, 36.5%) isolated enterovirus with peaks in 1999, 2002 and 2004. The other frequently isolated enteroviruses were Coxsackie virus type B (17 cases, 16.3%), echovirus 6 (11 cases, 10.6%), echovirus 11 (6 cases, 5.8%), and echovirus 13 (4 cases, 3.8 %). Mean hospitalization time was 6.2 ± 2.4 days. All patients recovered without any sequelae. Enteroviruses have an important role in childhood aseptic meningitis cases in Turkey too, and the predominant serotypes vary according to years.
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Tijsma, Aloys, David Franco, Simon Tucker, Rolf Hilgenfeld, Mathy Froeyen, Pieter Leyssen, and Johan Neyts. "The Capsid Binder Vapendavir and the Novel Protease Inhibitor SG85 Inhibit Enterovirus 71 Replication." Antimicrobial Agents and Chemotherapy 58, no. 11 (September 8, 2014): 6990–92. http://dx.doi.org/10.1128/aac.03328-14.
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ABSTRACTAntivirals against enterovirus 71 (EV71) are urgently needed. We demonstrate that the novel enteroviral protease inhibitor (PI) SG85 and capsid binder (CB) vapendavir efficiently inhibit thein vitroreplication of 21 EV71 strains/isolates that are representative of the different genogroups A, B, and C. The PI rupintrivir, the CB pirodavir, and the host-targeting compound enviroxime, which were included as reference compounds, also inhibited the replication of all isolates. Remarkably, the CB compound pleconaril was devoid of any anti-EV71 activity. Anin silicodocking study revealed that pleconaril—unlike vapendavir and pirodavir—lacks essential binding interactions with the viral capsid. Vapendavir and SG85 (or analogues) should be further explored for the treatment of EV71 infections. The data presented here may serve as a reference when developing yet-novel inhibitors.
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Netanyah, Eitan, Matteo Calafatti, Jeanette Arvastsson, Eduardo Cabrera-Rode, Corrado M. Cilio, and Luis Sarmiento. "Extracellular Vesicles Released by Enterovirus-Infected EndoC-βH1 Cells Mediate Non-Lytic Viral Spread." Microorganisms 8, no. 11 (November 8, 2020): 1753. http://dx.doi.org/10.3390/microorganisms8111753.
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While human enteroviruses are generally regarded as a lytic virus, and persistent non-cytolytic enterovirus infection in pancreatic beta cells has been suspected of playing a role in type 1 diabetes pathogenesis. However, it is still unclear how enteroviruses could exit the pancreatic beta cell in a non-lytic manner. This study aimed to investigate the role of beta cell-derived extracellular vesicles (EVs) in the non-lytic enteroviral spread and infection. Size-exclusion chromatography and antibody-based immunoaffinity purification were used to isolate EVs from echovirus 16-infected human beta EndoC-βH1 cells. EVs were then characterized using transmission electron microscopy and Multiplex Bead-Based Flow Cytometry Assay. Virus production and release were quantified by 50% cell culture infectious dose (CCID50) assay and qRT-PCR. Our results showed that EVs from echovirus 16-infected EndoC-βH1 cells harbor infectious viruses and promote their spread during the pre-lytic phase of infection. Furthermore, the EVs-mediated infection was not inhibited by virus-specific neutralizing antibodies. In summary, this study demonstrated that enteroviruses could exit beta cells non-lytically within infectious EVs, thereby thwarting the access of neutralizing antibodies to viral particles. These data suggest that enterovirus transmission through EVs may contribute to viral dissemination and immune evasion in persistently infected beta cells.