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1

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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2

Drummond, Coyne G., Alexa M. Bolock, Congrong Ma, Cliff J. Luke, Misty Good, and Carolyn B. Coyne. "Enteroviruses infect human enteroids and induce antiviral signaling in a cell lineage-specific manner." Proceedings of the National Academy of Sciences 114, no. 7 (January 30, 2017): 1672–77. http://dx.doi.org/10.1073/pnas.1617363114.

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Enteroviruses are among the most common viral infectious agents of humans and are primarily transmitted by the fecal–oral route. However, the events associated with enterovirus infections of the human gastrointestinal tract remain largely unknown. Here, we used stem cell-derived enteroids from human small intestines to study enterovirus infections of the intestinal epithelium. We found that enteroids were susceptible to infection by diverse enteroviruses, including echovirus 11 (E11), coxsackievirus B (CVB), and enterovirus 71 (EV71), and that contrary to an immortalized intestinal cell line, enteroids induced antiviral and inflammatory signaling pathways in response to infection in a virus-specific manner. Furthermore, using the Notch inhibitor dibenzazepine (DBZ) to drive cellular differentiation into secretory cell lineages, we show that although goblet cells resist E11 infection, enteroendocrine cells are permissive, suggesting that enteroviruses infect specific cell populations in the human intestine. Taken together, our studies provide insights into enterovirus infections of the human intestine, which could lead to the identification of novel therapeutic targets and/or strategies to prevent or treat infections by these highly clinically relevant viruses.
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3

Chapman, Nora M. "Persistent Enterovirus Infection: Little Deletions, Long Infections." Vaccines 10, no. 5 (May 12, 2022): 770. http://dx.doi.org/10.3390/vaccines10050770.

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Enteroviruses have now been shown to persist in cell cultures and in vivo by a novel mechanism involving the deletion of varying amounts of the 5′ terminal genomic region termed domain I (also known as the cloverleaf). Molecular clones of coxsackievirus B3 (CVB3) genomes with 5′ terminal deletions (TD) of varying length allow the study of these mutant populations, which are able to replicate in the complete absence of wildtype virus genomes. The study of TD enteroviruses has revealed numerous significant differences from canonical enteroviral biology. The deletions appear and become the dominant population when an enterovirus replicates in quiescent cell populations, but can also occur if one of the cis-acting replication elements of the genome (CRE-2C) is artificially mutated in the element’s stem and loop structures. This review discusses how the TD genomes arise, how they interact with the host, and their effects on host biology.
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4

Ayyub, Mohammed, Joshua George Thomas, and Rawad Hodeify. "An Overview of the Characteristics, Pathogenesis, Epidemiology, and Detection of Human Enterovirus in the Arabian Gulf Region." Viruses 16, no. 8 (July 24, 2024): 1187. http://dx.doi.org/10.3390/v16081187.

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Enteroviruses are RNA viruses that initiate infections through the gastrointestinal (GI) tract and are associated with enteric illness in individuals of all ages. Most serious infections of enteroviruses are in infants and young children where it is the common cause of aseptic meningitis and other systemic diseases, leading to a high mortality rate. Enteroviruses belong to the small non-enveloped family of the Picornaviridae family. The virus can spread mainly through fecal–oral and respiratory routes. In the Arabian Gulf countries, the incidence of enteroviral infections is only restricted to a few reports, and thus, knowledge of the epidemiology, characteristics, and pathogenesis of the virus in the gulf countries remains scarce. In this minireview, we sought to provide an overview of the characteristics of enterovirus and its pathogenesis, in addition to gathering the reports of enterovirus infection prevalence in Gulf Cooperation Council (GCC) countries. We also present a summary of the common methods used in its detection.
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5

Toczylowski, Kacper, Magdalena Wieczorek, Ewa Bojkiewicz, Magdalena Wietlicka-Piszcz, Beata Gad, and Artur Sulik. "Pediatric Enteroviral Central Nervous System Infections in Bialystok, Poland: Epidemiology, Viral Types, and Drivers of Seasonal Variation." Viruses 12, no. 8 (August 15, 2020): 893. http://dx.doi.org/10.3390/v12080893.

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Enteroviruses are common causes of infections of the central nervous system (CNS) that in temperate climates tend to peak in the summer. The aim of the study was to describe epidemiology, drivers of seasonality, and types of enteroviruses causing infections of the CNS in children in Northeastern Poland. We prospectively collected data on children hospitalized with infection of the CNS attributed to enteroviruses in Bialystok, Poland, from January 2015 to December 2019. In total, 224 children were included. Nineteen different enterovirus types were identified in isolates collected from 188 children. Coxsackie B5 (32%), echovirus 30 (20%), and echovirus 6 (14%) were the three most common types. Enteroviruses were more prevalent during the summer–fall season. Infections caused by echovirus 30 peaked early in June and coxsackievirus B5 in July, whereas echovirus 6 peaked late in October. Phylogenetic analyses of these three enterovirus types showed multiple lineages co-circulating in this region. Mean air temperatures and precipitation rates were independently associated with monthly number of cases. Considering lack of effective treatment or vaccine, easy transmission of enteroviruses between susceptible individuals, their high mutation rate and prolonged time of viral shedding, continued monitoring and surveillance are imperative to recognize enteroviral infections of the CNS and the changes in circulation of enteroviruses in Poland.
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6

Zhukova, L. I., G. K. Rafeenko, V. N. Gorodin, and A. A. Vanyukov. "CLINICAL-EPIDEMIOLOGICAL CHARACTERISTICS OF ENTEROVIRUS NONPOLIOMIELITIS INFECTIONS IN THE KRASNODAR TERRITORY." Journal of microbiology epidemiology immunobiology, no. 5 (October 28, 2018): 9–15. http://dx.doi.org/10.36233/0372-9311-2018-5-9-15.

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Aim. To characterize the epidemic situation and the clinical course of enterovirus (neolio) infections in the Krasnodar Territory. Materials and methods. Retrospective analysis of manifestations of the epidemic process and clinical characteristics of non-poliomyelitis enterovirus infections from 2002 to 2017 in the territory of the Krasnodar Territory. Results. The incidence of enterovirus infections, the structure of clinical forms, the landscape of enteroviruses isolated from the environment and the biological material of patients was demonstrated. The clinical course of enterovirus infection in 170 hospitalized patients was characterized. Conclusion. Enterovirus (nepolio) infection in the Krasnodar Territory in many years of dynamics demonstrates growing relevance. A variety of enterovirus serotypes circulating in the environment and in the human population are preserved, the spectrum of which varies. In the structure of clinical forms of enterovirus infections, the number of diseases without affecting the central nervous system increases, which indicates an improvement in the quality of diagnosis and an increase in the diagnostic motivation of doctors. Further measures for epidemiological surveillance, as well as training of physicians of various specialties, are expedient, which will help to increase the effectiveness of diagnosis and treatment of enterovirus (nepolio) infection.
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7

Golitsyna, L. N., T. T. T. Nguyen, N. I. Romanenkova, M. T. Luong, L. T. Vu, O. I. Kanaeva, M. A. Bichurina, and N. A. Novikova. "Enterovirus infection in the Socialist Republic of Vietnam." Russian Journal of Infection and Immunity 9, no. 3-4 (November 15, 2019): 467–75. http://dx.doi.org/10.15789/2220-7619-2019-3-4-467-475.

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Human enterovirus infections comprise a group of infectious diseases caused by viruses of Enterovirus A-D species (genus Enterovirus, family Picornaviridae). Enterovirus infections can vary in clinical manifestations and severity, from asymptomatic infection to serious multisystem diseases. During evolution, enterovirus strains with increased neurovirulence or atypical pathogenicity may emerge exhibiting an epidemic potential. Recently, outbreaks of enterovirus infection with an increased rate of neurological manifestations, a significant percentage of severe cases and lethal outcomes have been observed worldwide, which were associated with enteroviruses EV-A71, EV-D68 etc. The World Health Organization has included EV-A71 and EV-D68 enterovirus infection together with some other dangerous viral diseases considered for inclusion in the List of Blueprint Priority Diseases. In connection with this, global enterovirus surveillance is important for controlling emergence and spread of epidemic enterovirus variants, prediction of establishing epidemic situation, timely conduction of preventive measures and vaccine development. A growing multi-field cooperation between Russia and Vietnam leads to increased two-way population migration, which actualizes scientific and practical collaboration in surveillance and control of infectious disease spread, including enterovirus infection. Currently, epidemiological surveillance of enterovirus infection in Vietnam is based on monitoring hand, foot and mouth disease (HFMD) rate, laboratory diagnostics of enterovirus infection and identification of enterovirus strains, mainly detected in severe patients. In 2001–2016, 34 non-polio virus types were identified in patients with enterovirus infection, largely represented by viruses EV-A71, CVA6, CVA10, and CVA16. Moreover, the peak incidence of enterovirus infection and related mortality rate were associated with the increased activity of EV-A71 virus. In Vietnam, EVA71 enterovirus of genotypes C1, C4, C5 and B5 circulated at different times. Over the last years, a new pandemic genotype virus CVA6 has been dominating as a causative agent of enterovirus infection in Vietnam as well as the majority of other countries. The data on phylogenetic relation between Vietnamese epidemic EV-A71 and CVA6 strains allowed to find that they underwent multiple betweencountry spreads, whereas their subsequent in-country dissemination resulted in 2011–2012 enterovirus outbreak and sustained high-level HFMD morbidity.
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8

Wells, Alexandra I., and Carolyn B. Coyne. "Enteroviruses: A Gut-Wrenching Game of Entry, Detection, and Evasion." Viruses 11, no. 5 (May 21, 2019): 460. http://dx.doi.org/10.3390/v11050460.

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Enteroviruses are a major source of human disease, particularly in neonates and young children where infections can range from acute, self-limited febrile illness to meningitis, endocarditis, hepatitis, and acute flaccid myelitis. The enterovirus genus includes poliovirus, coxsackieviruses, echoviruses, enterovirus 71, and enterovirus D68. Enteroviruses primarily infect by the fecal–oral route and target the gastrointestinal epithelium early during their life cycles. In addition, spread via the respiratory tract is possible and some enteroviruses such as enterovirus D68 are preferentially spread via this route. Once internalized, enteroviruses are detected by intracellular proteins that recognize common viral features and trigger antiviral innate immune signaling. However, co-evolution of enteroviruses with humans has allowed them to develop strategies to evade detection or disrupt signaling. In this review, we will discuss how enteroviruses infect the gastrointestinal tract, the mechanisms by which cells detect enterovirus infections, and the strategies enteroviruses use to escape this detection.
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9

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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10

van Ackeren, Vanessa, Stefan Schmutz, Ian Pichler, Gabriela Ziltener, Maryam Zaheri, Verena Kufner, and Michael Huber. "Retrospective Genotyping of Enteroviruses Using a Diagnostic Nanopore Sequencing Workflow." Pathogens 13, no. 5 (May 8, 2024): 390. http://dx.doi.org/10.3390/pathogens13050390.

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Enteroviruses are among the most common viruses pathogenic to humans. They are associated with various forms of disease, ranging from mild respiratory illness to severe neurological diseases. In recent years, an increasing number of isolated cases of children developing meningitis or encephalitis as a result of enterovirus infection have been reported, as well as discrete enterovirus D68 outbreaks in North America in 2014 and 2016. We developed an assay to rapidly genotype enteroviruses by sequencing a region within the VP1 gene using nanopore Flongles. We retrospectively analyzed enterovirus-/rhinovirus-positive clinical samples from the Zurich, Switzerland area mainly collected during two seasons in 2019/2020 and 2021/2022. Respiratory, cerebrospinal fluid, and stool samples were analyzed. Whole-genome sequencing was performed on samples with ambiguous genotyping results and enterovirus D68-positive samples. Out of 255 isolates, a total of 95 different genotypes were found. A difference in the prevalence of enterovirus and rhinovirus infections was observed for both sample type and age group. In particular, children aged 0–4 years showed a higher frequency of enterovirus infections. Comparing the respiratory seasons, a higher prevalence was found, especially for enterovirus A and rhinovirus A after the SARS-CoV-2 pandemic. The enterovirus genotyping workflow provides a rapid diagnostic tool for individual analysis and continuous enterovirus surveillance.
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11

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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12

Adekolujo, Daniel R., Suraj O. Olayinka, Johnson A. Adeniji, Oyetunde T. Oyeyemi, and Alexander B. Odaibo. "Poliovirus and other enteroviruses in children infected with intestinal parasites in Nigeria." Journal of Infection in Developing Countries 9, no. 10 (October 29, 2015): 1166–71. http://dx.doi.org/10.3855/jidc.5863.

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Introduction: Poliovirus, an enterovirus, still persists in Nigeria despite the global efforts tailored towards its eradication. This study aimed to assess the impacts of poliovirus and other enteroviruses on the susceptibility of individuals to intestinal parasite infections. Methodology: A cross-sectional study on the prevalence of intestinal parasites was conducted on two-sample stool specimens of 717 Nigerian children (between 1 and 19 years of age) whose poliovirus/other enteroviruses infection status had been determined. Results: The overall prevalence of Sabin poliovirus and other related enteroviruses infections were 6.6% and 13.8%, respectively. The prevalence of Ascaris lumbricoides was significantly higher than that of other intestinal parasites (p < 0.05), with children in the 0–4 year age group being the most predisposed age group to intestinal parasitic infection (OR = 11.7, CI = 9.2–15.0). While the prevalence of all species of parasites except S. mansoni showed no significant variations in children with Sabin poliovirus (p > 0.05), the prevalence of hookworms and Taenia spp. was significantly higher in children with other enteroviral infections (p < 0.05). Conclusions: The high risk of children of acquiring enteroviral infection through some intestinal parasites is an indication of possible association of the parasites in a more poliovirus-endemic population. A combined intervention approach for the two infections is advocated.
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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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Romanenkova, Natalia I., Thi Thanh Thao Nguyen, Liudmila N. Golitsyna, Natalia V. Ponomareva, Nadezhda R. Rozaeva, Olga I. Kanaeva, Artem V. Leonov, Nadezhda A. Novikova, and Maina A. Bichurina. "Enterovirus 71-Associated Infection in South Vietnam: Vaccination Is a Real Solution." Vaccines 11, no. 5 (May 3, 2023): 931. http://dx.doi.org/10.3390/vaccines11050931.

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Hand-foot-and-mouth disease (HFMD) is the most common enteroviral infection in South-East Asia. When evaluating the role of enterovirus 71 (EVA71) as an etiological agent of infectious disease in South Vietnam, we revealed a high proportion of EVA71 among identified species A enteroviruses found in 3542 samples from HFMD cases; 125 samples from cases of enteroviral meningitis; and 130 samples from acute flaccid paralysis (AFP) cases. These represent 50%, 54.8%, and 51.5%, respectively. According to molecular analysis, 90% of EVA71 were attributed to genotype C4 and 10% were attributed to genotype B5. The predominance of EVA71 circulation among the population proves the need to strengthen surveillance (with monitoring of enterovirus circulation for facilitation of HFMD outbreak prediction) and to increase the effectiveness of preventative measures by the implementation of vaccination against EVA71-associated infections. A phase III trial of a Taiwanese vaccine (EV71vac) in Taiwan and South Vietnam showed its safety, tolerability, and efficacy in children aged 2–71 months. This B4 genotype-based vaccine, which features cross-protection against B5 and C4 genotypes, and other existing EV71 vaccines can serve as a good approach to solving the HFMD problem, which is so important for Vietnam.
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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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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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Di Cristanziano, Veronica, Kristina Weimer, Sindy Böttcher, Fred Stephen Sarfo, Albert Dompreh, Lucio-Garcia Cesar, Elena Knops, et al. "Molecular Characterization and Clinical Description of Non-Polio Enteroviruses Detected in Stool Samples from HIV-Positive and HIV-Negative Adults in Ghana." Viruses 12, no. 2 (February 16, 2020): 221. http://dx.doi.org/10.3390/v12020221.

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In the post-polio eradication era, increasing attention is given to non-polio enteroviruses. Most of the data about enteroviruses in sub-Saharan Africa are related to acute flaccid paralysis surveillance and target the pediatric population. This study aimed to investigate the presence of enterovirus in PLHIV (people living with HIV) and HIV-negative individuals in Ghana. Stool samples from HIV-positive individuals (n = 250) and healthy blood donors (n = 102) attending the Komfo Anokye Teaching Hospital in Kumasi, Ghana, were screened by real-time PCR for enterovirus. Molecular typing of the VP1 region was performed. Enterovirus-positive samples were tested for norovirus, adenovirus, rotavirus, sapovirus, and cosaviruses. Twenty-six out of 250 HIV-positive subjects (10.4%) and 14 out of 102 HIV-negative individuals (13.7%) were detected enterovirus-positive, not showing a significant different infection rate between the two groups. HIV-negative individuals were infected with Enterovirus C strains only. HIV-positive participants were detected positive for species Enterovirus A, Enterovirus B, and Enterovirus C. Co-infections with other viral enteric pathogens were almost exclusively detected among HIV-positive participants. Overall, the present study provides the first data about enteroviruses within HIV-positive and HIV-negative adults living in Ghana.
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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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19

PORTES, Silvana A. R., Edson E. DA SILVA, Marilda M. SIQUEIRA, Ana Maria B. DE FILIPPIS, Murilo M. KRAWCZUK, and Jussara P. NASCIMENTO. "ENTEROVIRUSES ISOLATED FROM PATIENTS WITH ACUTE RESPIRATORY INFECTIONS DURING SEVEN YEARS IN RIO DE JANEIRO (1985-1991)." Revista do Instituto de Medicina Tropical de São Paulo 40, no. 6 (November 1998): 337–42. http://dx.doi.org/10.1590/s0036-46651998000600001.

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Enteroviruses were investigated in respiratory secretions collected from patients with acute respiratory infections (ARI) over a seven year period (1985-1991), as part of a longitudinal study of ARI aetiology. All the viruses that are most commonly associated with ARI were found in this study. Among the virus isolates, enteroviruses were only less frequent than respiratory syncytial viruses, adenoviruses and influenzaviruses. Forty five enterovirus samples were isolated from patients with either upper respiratory tract infections (URTI) or lower respiratory tract infections (LRTI). From these enterovirus isolates, thirty one samples were identified as poliovirus (n=18) and non polio enterovirus (n=13) by serum neutralization. Poliovirus were identified as type 1 and 2 and all of them were vaccinal strains. From thirteen non polio enterovirus, twelve were identified as echovirus serotypes 1, 2, 7, 11, 19 and 31. The remainder was identified as coxsackievirus B4.
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Precechtelova, Jana, Maria Borsanyiova, Sona Sarmirova, and Shubhada Bopegamage. "Type I Diabetes Mellitus: Genetic Factors and Presumptive Enteroviral Etiology or Protection." Journal of Pathogens 2014 (2014): 1–21. http://dx.doi.org/10.1155/2014/738512.

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We review type 1 diabetes and host genetic components, as well as epigenetics and viruses associated with type 1 diabetes, with added emphasis on the enteroviruses, which are often associated with triggering the disease. GenusEnterovirusis classified into twelve species of which seven (Enterovirus A, Enterovirus B, Enterovirus C,andEnterovirus DandRhinovirus A, Rhinovirus B,andRhinovirus C) are human pathogens. These viruses are transmitted mainly by the fecal-oral route; they may also spread via the nasopharyngeal route. Enterovirus infections are highly prevalent, but these infections are usually subclinical or cause a mild flu-like illness. However, infections caused by enteroviruses can sometimes be serious, with manifestations of meningoencephalitis, paralysis, myocarditis, and in neonates a fulminant sepsis-like syndrome. These viruses are often implicated in chronic (inflammatory) diseases as chronic myocarditis, chronic pancreatitis, and type 1 diabetes. In this review we discuss the currently suggested mechanisms involved in the viral induction of type 1 diabetes. We recapitulate current basic knowledge and definitions.
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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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Tsang, Jessica Oi-Ling, Jie Zhou, Xiaoyu Zhao, Cun Li, Zijiao Zou, Feifei Yin, Shuofeng Yuan, Man-Lung Yeung, Hin Chu, and Jasper Fuk-Woo Chan. "Development of Three-Dimensional Human Intestinal Organoids as a Physiologically Relevant Model for Characterizing the Viral Replication Kinetics and Antiviral Susceptibility of Enteroviruses." Biomedicines 9, no. 1 (January 18, 2021): 88. http://dx.doi.org/10.3390/biomedicines9010088.

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Enteroviruses are important causes of hand, foot, and mouth disease, respiratory infections, and neurological infections in human. A major hurdle for the development of anti-enterovirus agents is the lack of physiologically relevant evaluation platforms that closely correlate with the in vivo state. We established the human small intestinal organoids as a novel platform for characterizing the viral replication kinetics and evaluating candidate antivirals for enteroviruses. The organoids supported productive replication of enterovirus (EV)-A71, coxsackievirus B2, and poliovirus type 3, as evidenced by increasing viral loads, infectious virus titers, and the presence of cytopathic effects. In contrast, EV-D68, which mainly causes respiratory tract infection in humans, did not replicate significantly in the organoids. The differential expression profiles of the receptors for these enteroviruses correlated with their replication kinetics. Using itraconazole as control, we showed that the results of various antiviral assays, including viral load reduction, plaque reduction, and cytopathic effect inhibition assays, were highly reproducible in the organoids. Moreover, itraconazole attenuated virus-induced inflammatory response in the organoids, which helped to explain its antiviral effects and mechanism. Collectively, these data showed that the human small intestinal organoids may serve as a robust platform for investigating the pathogenesis and evaluating antivirals for enteroviruses.
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Pasquinelli, L., and C. Byington. "Enterovirus Infections." Pediatrics in Review 27, no. 2 (February 1, 2006): e14-e15. http://dx.doi.org/10.1542/pir.27-2-e14.

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Zaoutis, T., and J. D. Klein. "Enterovirus Infections." Pediatrics in Review 19, no. 6 (June 1, 1998): 183–91. http://dx.doi.org/10.1542/pir.19-6-183.

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Noor, A., and L. R. Krilov. "Enterovirus Infections." Pediatrics in Review 37, no. 12 (December 1, 2016): 505–15. http://dx.doi.org/10.1542/pir.2016-0103.

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Zaoutis, Theoklis, and Joel D. Klein. "Enterovirus Infections." Pediatrics In Review 19, no. 6 (June 1, 1998): 183–91. http://dx.doi.org/10.1542/pir.19.6.183.

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Pasquinelli, L. "Enterovirus Infections." Pediatrics In Review 27, no. 2 (February 1, 2006): e14-e15. http://dx.doi.org/10.1542/pir.27.2.e14.

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28

Selivanova, Svetlana G., Vladimir V. Zverev, Natalya V. Ponomareva, Artem V. Leonov, Alexander Yu Kashnikov, Natalia V. Epifanova, Anastasia V. Polyanina, and Nadezhda A. Novikova. "Detection and type identification of non-polio enteroviruses in children against the background of acute intestinal infections of various etiologies: 2018–2023." Journal of microbiology, epidemiology and immunobiology 101, no. 3 (July 16, 2024): 351–61. http://dx.doi.org/10.36233/0372-9311-513.

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Introduction. Enteroviruses (EV) are characterized by: species and type diversity, polymorphism of clinical manifestations, a tendency to epidemic spread, and are often the cause of disease outbreaks, which determines the relevance of monitoring EV strains in various clinical forms of infection, including in conditions of anti-epidemic measures. The aim of the study: to characterize the prevalence and diversity of non-polio enteroviruses (NPEV) types in children with acute intestinal infection (AII) in the period 2018–2023, including the COVID-19 pandemic. Materials and methods. The RT-PCR method was used to study 7302 samples of feces from children hospitalized with a diagnosis of AII in the infectious diseases hospital of Nizhny Novgorod. Genotyping of EV strains was carried out using fragment Sanger sequencing of the genome region encoding capsid protein 1 (VP1) and the online resource BLAST. Results. EVs were found in 5.0 ± 0.3% (1.7–7.8%), both in mono- and mixed infections with other enteric viruses. The long-term dynamics of the frequency of EV detection and the incidence of EV infection in children in the Nizhny Novgorod region was characterized by a sharp decrease in indicators in 2020 against the backdrop of the introduction of anti-epidemic measures. When genotyping 299 strains, 41 types of NPEV of 4 species were identified. The spectrum included the main pathogens of exanthema and neuroinfections and rare types found in “minor” or intestinal forms of infection. During the study period, a redistribution of NPEV species was established. Before the pandemic, the ratio of Enterovirus A : Enterovirus B : Enterovirus C species was as follows — 41.0 : 46.7 : 12.3%; during the 2020 pandemic season the ratio was 0.0 : 37.5 : 62.5%; after the lifting of restrictive measures — 47 : 29 : 23%, which may be due to the different effectiveness of the restrictive measures on the mechanisms of transmission of EVs of different types. Conclusion. The genetic diversity of NPEVs detected in children with AII complements information on the typical composition of the territorial enterovirus population. In children with AII, when the airborne transmission of SARS-CoV-2 was blocked, there was a decrease in the frequency of detection of viruses of the Enterovirus B type, the absence of detection of Enterovirus A and the constant presence of Enterovirus C.
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Donelan, Susan V., Silvia Spitzer, and Eric Spitzer. "2799. Inability to Locally Differentiate Rhinovirus/Enterovirus Results Impacts Infection Control Practices." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S989—S990. http://dx.doi.org/10.1093/ofid/ofz360.2476.

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Abstract Background Rhinoviruses and Enteroviruses are closely related members of the family picornavirideae; however, they have distinct clinical manifestations. Rhinoviruses cause respiratory infections while Enteroviruses often present as nonspecific febrile illnesses. Enterovirus D68 (EV-D68) is unusual in that although it is classified as an enterovirus it causes respiratory illness. Most of the currently used nucleic acid amplification assays for respiratory viruses do not distinguish between Rhino and Enteroviruses because of their shared homology. Rhino/Enterovirus infections are common in the Summer and Fall. In October of 2018 the NYS DOH issued a health advisory describing increased numbers of EV-D68 infection. Although there is no specific treatment for EV-D68, the advisory recommended contact precautions in addition to the droplet precautions recommended for other respiratory viruses. This recommendation creates logistical difficulties since there are no commercial test-kits that can identify EV-D68. The aim of this study was to determine the incidence of EV-D68 among patients admitted to Stony Brook Hospital that tested positive for Rhino/Enterovirus. Methods Nasopharyngeal swabs were tested with the BioFire® FilmArray® Respiratory Panel (RP 2) test. 44 Rhino/Enterovirus positive specimens were sent for further identification to the NYS DOH Virology Lab. Enterovirus was differentiated from Rhinovirus by qRT–PCR. EV-D68 was identified by sequencing. Results During one week in October, 10 patients were admitted with positive EV-D68 (5 adults and 5 children). In contrast, all 21 admitted patients who had specimens sent for typing had Rhinovirus. Conclusion This study confirmed that there was significant EV-D68 activity among patients who required hospitalization consistent with the NYS DOH advisory in the Fall of 2018. In contrast, in the Winter a drop in the prevalence of Rhino/enterovirus was observed. EV-D68 was not found in any of the samples sent for typing. These data informed our internal decision to cohort all patients this past Winter with positive Rhino/enterovirus results, positively impacting patient cohorting capabilities during a time with increased local influenza activity. 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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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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Lloyd, Richard E., Manasi Tamhankar, and Åke Lernmark. "Enteroviruses and Type 1 Diabetes: Multiple Mechanisms and Factors?" Annual Review of Medicine 73, no. 1 (January 27, 2022): 483–99. http://dx.doi.org/10.1146/annurev-med-042320-015952.

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Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by insulin deficiency and resultant hyperglycemia. Complex interactions of genetic and environmental factors trigger the onset of autoimmune mechanisms responsible for development of autoimmunity to β cell antigens and subsequent development of T1D. A potential role of virus infections has long been hypothesized, and growing evidence continues to implicate enteroviruses as the most probable triggering viruses. Recent studies have strengthened the association between enteroviruses and development of autoimmunity in T1D patients, potentially through persistent infections. Enterovirus infections may contribute to different stages of disease development. We review data from both human cohort studies and experimental research exploring the potential roles and molecular mechanisms by which enterovirus infections can impact disease outcome.
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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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Tkhakushinova, N. Kh, T. T. Shaturina, L. A. Ledenko, and O. V. Bevzenko. "Enterovirus infection in children in the Krasnodar Region, clinical and epidemiological characteristics." Infekcionnye bolezni 18, no. 4 (2020): 105–8. http://dx.doi.org/10.20953/1729-9225-2020-4-105-108.

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Objective. To analyze age-specific etiology and clinical manifestations of enteroviral infections (EVIs) in children residing in Krasnodar region. Patients and methods. This retrospective study included 3,213 patients with confirmed EVIs registered between 2006 and 2018 and admitted to the Specialized Clinical Children's Hospital for Infectious Diseases. Polymerase chain reaction was used to confirm the diagnosis. Results. We found that the most common enteroviruses circulating in Krasnodar region for many years were Coxsackie B virus and ECHO viruses 6, 11, and 30. The majority of patients (75.1%) had isolated forms of infection. Almost one-third of children (27.8%) demonstrated central nervous system lesions (primarily meningitis) that were more common in children aged 3 to 12 years. Other clinical forms were observed in young children. Almost all children hospitalized (91%) attended kindergartens. Conclusion. Coxsackie B virus and ECHO viruses 6, 11, and 30 have been circulating in Krasnodar region for the last 12 years; enterovirus type 71 has recently been found in this area. The highest proportion of EVI cases requiring inpatient treatment was observed among young children, in whom EVIs primarily manifested with meningitis. Primary school children usually had herpangina and exanthema, while older children developed epidemic myalgia. Our findings indicate the need for a set of measures aimed at reducing the incidence of EVIs among children of Krasnodar region. Key words: children, enteroviral infection, Krasnodar region, epidemiology, clinical manifestations, diagnosis
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Modlin, John F., Ron Dagan, Linda E. Berlin, David M. Virshup, Robert H. Yolken, and Marilyn Menegus. "Focal Encephalitis With Enterovirus Infections." Pediatrics 88, no. 4 (October 1, 1991): 841–45. http://dx.doi.org/10.1542/peds.88.4.841.

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We report on four pediatric patients with Enterovirus infections who were admitted to the hospital with signs or symptoms of acute, focal encephalitis. All four experienced focal seizures. Each had a cerebrospinal fluid pleocytosis at the initial lumbar puncture. In all four patients the diagnosis of herpes simplex encephalitis was entertained. Each child improved spontaneously within a few days of admission to the hospital, and only one had residual neurologic abnormalities at the time of discharge. A brief review of these cases, and three addditional cases from the literature, indicate that the enteroviruses, particularly the group A Coxsackieviruses, are rare causes of acute focal encephalitis in children and adolescents.
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Bopegamage, Shubhada. "ENTEROVIRUS INFECTIONS IN NEONATES AND CHILDREN." Інфекційні хвороби, no. 1 (May 18, 2020): 60–63. http://dx.doi.org/10.11603/1681-2727.2020.1.11108.

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Enteroviruses are prevalent globally. They are transmitted by the fecal oral route and also the respiratory route. Although these viruses cause mild febrile symptoms in immunocompetent humans, their infections result in a wide range of diseases in the neonates and young infants. The pathogenesis of these viruses depends on the host and virus factors. This mini-review makes the readers aware of the seriousness of enterovirus infections in the pediatric population, and to show the necessity of the molecular diagnostics.
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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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Melnichenko, O. M., A. Yu Yushchenko, Z. S. Klestova, O. M. Deryabin, O. S. Vatlitsova, and A. M. Golovko. "THE CULTURAL PROPERTIES ALTERATIONS OF PORCINE ENTEROVIRUS DURING LONG-TERM STORAGE." Scientific and Technical Bulletin оf State Scientific Research Control Institute of Veterinary Medical Products and Fodder Additives аnd Institute of Animal Biology 21, no. 2 (October 27, 2020): 123–36. http://dx.doi.org/10.36359/scivp.2020-21-2.17.

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Enterovirus infections remain one of the urgent problems in modern infectious pathology and are represented in numerous publications of domestic and foreign researchers, including publications in the field of veterinary virology. The causative agents of enterovirus infections of viral etiology (enteroviruses) are characterized by relative resistance to adverse environmental conditions, including thermal stability, acid resistance, resistance to proteolytic enzymes, which allows them to survive in the environment and facilitates their transmission by various ecological routes (water, food, aerosols, contaminated objects, etc.). The purpose of this study was to elucidate the changes in the infectious properties of porcine enteroviruses in vitro under conditions of long-term storage at a temperature of minus 32 °C. In the course of this study, a re- cultivation process was carried out with the subsequent adaptation of two variants of viruses: the porcine teschovirus of the first serotype (Teschovirus A), the “Dniprovsky 34” strain and Porcine sapelovirus 1 (porcine enterovirus of serogroup 8), the reference V-13 strain. The re-cultivation was performed on BHK-21 cell cultures / clone 13 and on SPEV, in which they were previously cultivated, in order to determine the infectious activity after storage under negative temperatures (minus 32 °C) for two and twenty years. On the example of porcine enterovirus of serogroup 8 (the causative agent of viral gastroenteritis), it was proved that during long-term storage (20 years) at a temperature of – 32 °C, the virus did not lose its infectious properties, although a change in the cytopathogenic effect in vitro during re-cultivation was found. The infectious properties of the porcine teshovirus of the first serotype are also capable of long-term storage (2 years) under conditions of minus 32 °C temperature.
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Moghimi, Seyedehmahsa, Ekaterina Viktorova, Anna Zimina, Tomasz Szul, Elizabeth Sztul, and George A. Belov. "Enterovirus Infection Induces Massive Recruitment of All Isoforms of Small Cellular Arf GTPases to the Replication Organelles." Journal of Virology 95, no. 2 (October 21, 2020): e01629-20. http://dx.doi.org/10.1128/jvi.01629-20.

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ABSTRACTEnterovirus replication requires the cellular protein GBF1, a guanine nucleotide exchange factor for small Arf GTPases. When activated, Arfs associate with membranes, where they regulate numerous steps of membrane homeostasis. The requirement for GBF1 implies that Arfs are important for replication, but which of the different Arfs function(s) during replication remains poorly understood. Here, we established cell lines expressing each of the human Arfs fused to a fluorescent tag and investigated their behavior during enterovirus infection. Arf1 was the first to be recruited to the replication organelles, where it strongly colocalized with the viral antigen 2B and mature virions but not double-stranded RNA. By the end of the infectious cycle, Arf3, Arf4, Arf5, and Arf6 were also concentrated on the replication organelles. Once on the replication membranes, all Arfs except Arf3 were no longer sensitive to inhibition of GBF1, suggesting that in infected cells they do not actively cycle between GTP- and GDP-bound states. Only the depletion of Arf1, but not other class 1 and 2 Arfs, significantly increased the sensitivity of replication to GBF1 inhibition. Surprisingly, depletion of Arf6, a class 3 Arf, normally implicated in plasma membrane events, also increased the sensitivity to GBF1 inhibition. Together, our results suggest that GBF1-dependent Arf1 activation directly supports the development and/or functioning of the replication complexes and that Arf6 plays a previously unappreciated role in viral replication. Our data reveal a complex pattern of Arf activation in enterovirus-infected cells that may contribute to the resilience of viral replication in different cellular environments.IMPORTANCE Enteroviruses include many known and emerging pathogens, such as poliovirus, enteroviruses 71 and D68, and others. However, licensed vaccines are available only against poliovirus and enterovirus 71, and specific anti-enterovirus therapeutics are lacking. Enterovirus infection induces the massive remodeling of intracellular membranes and the development of specialized domains harboring viral replication complexes, replication organelles. Here, we investigated the roles of small Arf GTPases during enterovirus infection. Arfs control distinct steps in intracellular membrane traffic, and one of the Arf-activating proteins, GBF1, is a cellular factor required for enterovirus replication. We found that all Arfs expressed in human cells, including Arf6, normally associated with the plasma membrane, are recruited to the replication organelles and that Arf1 appears to be the most important Arf for enterovirus replication. These results document the rewiring of the cellular membrane pathways in infected cells and may provide new ways of controlling enterovirus infections.
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Jarzynski, Adrian, Agata Dubas, and Malgorzata Polz-Dacewicz. "The prevalence of enteroviruses that cause respiratory infections in patients with influenzavirus A/H1N1 hospitalized in the Lublin province." Current Issues in Pharmacy and Medical Sciences 27, no. 3 (September 1, 2014): 199–201. http://dx.doi.org/10.1515/cipms-2015-0015.

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ABSTRACT Viruses that cause respiratory tract infections are the most common agents of infectious diseases in humans throughout the world. A virus that infects the respiratory system, may induce various clinical symptoms. What is more, the same symptoms may be caused by different viruses. The aim of the study was to analyze the prevalence of enteroviruses that cause respiratory infections in patients with influenzavirus A/H1N1 hospitalized in the Lublin province. The experimental material was throat and nose swabs taken from patients hospitalized in Lublin and Tomaszow Lubelski. In the group of 44 patients (20 women and 24 men) infected with influenza A/H1N1, the genetic material of enteroviruses was detected in 13 patients (29.5%). Respiratory viruses co-infections are very common in hospitalized patients. Studies show that co-infection with influenza virus and enterovirus are more common in children than in adults. Moreover, viral respiratory tract infections are independent from the patients’ gender.
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Tkhakushinova, N. Kh, and T. T. Shaturina. "Enterovirus infections: current state of the problem." Infekcionnye bolezni 20, no. 3 (2022): 92–97. http://dx.doi.org/10.20953/1729-9225-2022-3-92-97.

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In this review, we analyze the whole spectrum of the current state of the problem of enterovirus infection in the world and in one of the regions of the Russian Federation, namely Krasnodar region. We discuss the currently used classification of enterovirus infections, clinical manifestations, new approaches to diagnosis, treatment, and prevention. Key words: enterovirus infection, serotype, poliovirus
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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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Piriyapornpipat, Sukhum, C. Pittayawonganon, A. Mungaomklang, J. Prasertsopon, H. Praekunatham, O. Arjkumpa, S. Wechwithan, et al. "Investigation of A Severe Enteroviral Encephalitis and Circulating Genotypes during Hand, Foot and Mouth Disease Surge in Nakhon Ratchasima Province, Thailand, August 2011." Outbreak, Surveillance, Investigation & Response (OSIR) Journal 7, no. 1 (March 31, 2014): 16–22. http://dx.doi.org/10.59096/osir.v7i1.263295.

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On 7 Aug 2011, a 1-month-old baby with encephalitis caused by unspecified enterovirus was reported during the period of widespread hand, foot and mouth disease (HFMD) outbreaks in Nakhon Ratchasima Province. An investigation was carried out to confirm the diagnosis, identify etiology of all severe enteroviral infection cases, determine magnitude of HFMD and enterovirus infection, including asymptomatic infections, and recommend prevention and control measures. A descriptive study was conducted by interviewing family members of the index case. Throat swab and stool specimens were collected to identify enterovirus. Survey on asymptomatic infection was done in schools attended by the index case’s siblings. Stool culture and isolation for enterovirus were also performed. Coxsackie B5 virus was isolated from fresh stool specimens of the index case. Among total 244 students screened for HFMD symptoms in four schools, only seven (3%) met the suspect case definition. During HFMD outbreaks caused by EV-71 B5, coxsackie A16 and coxsackie B5, proportion of asymptomatic infection among students was 22%. Risk factors such as no soap in toilets and misuse of alcohol gel to clean hands in schools were observed during the environmental survey.
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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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Madeddu, Silvia, Roberta Ibba, Giuseppina Sanna, Sandra Piras, Federico Riu, Alessandra Marongiu, Annalisa Ambrosino, et al. "Human Enterovirus B: Selective Inhibition by Quinoxaline Derivatives and Bioinformatic RNA-Motif Identification as New Targets." Pharmaceuticals 15, no. 2 (January 31, 2022): 181. http://dx.doi.org/10.3390/ph15020181.

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The Enterovirus genus includes many viruses that are pathogenic in humans, including Coxsackie viruses and rhinoviruses, as well as the emerging enteroviruses D68 and A71. Currently, effective antiviral agents are not available for the treatment or prevention of enterovirus infections, which remain an important threat to public health. We recently identified a series of quinoxaline derivatives that were provento be potent inhibitors of coxsackievirus B5, the most common and a very important human pathogen belonging to the enterovirus genus. We have shown how most active derivatives interfere with the earliest stages of viral replication, blocking infection. Considering the broad antiviral spectrum, a very attractive property for an antiviral drug, we aimed to investigate the antiviral activity of the most promising compounds against other Enterovirus species. Here, we investigated the susceptibility of a panel of representatives of Enterovirus genus (enterovirus A71, belonging to A species; coxsackieviruses B4 and B3;echovirus 9, belonging to B species; and enterovirus D68, belonging to D species) to quinoxaline inhibitors. We also tested cytotoxicity and selectivity indices of the selected compounds, as well as their effects on virus yield.We also investigated their potential mechanism of action by a time course assay. In addition, a bioinformatic analysis was carried out to discover potential new conserved motifs in CVB3 and CVB4 compared to the other enterovirus species that can be used as new targets.
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Shih, Tzu-Ching, and Po-Yuan Chen. "THE RECOMBINATION OF HUMAN ENTEROVIRUS 71." Biomedical Engineering: Applications, Basis and Communications 19, no. 05 (October 2007): 295–301. http://dx.doi.org/10.4015/s1016237207000392.

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In 1998, the enterovirus (EV) infections outbreak in Taiwan caused 78 fatalities. Since then, EV infections have continuously posed a threat to the public. Among the 64 serotypes of enteroviruses known to infect human, the enterovirus 71(EV71) is suspected to be the major cause for severe cases. In this study, we estimate the recombination point of enterovirus 71 vp1 by using the method of Likelihood Analysis of Recombination in DNA. The datasets of enterovirus 71 DNA sequences are available in GenBank. After careful cross validation, eight candidate sequences are chosen to advance analysis, including 2734TAI98, TW227298, 1423SIN98 and other five DNA sequences as well. Then, the construction of the phylogeny trees (neighbor-joining trees will be used in this paper) would support for recombination in EV71 virus. In these two methods, the breakpoint was found to be in similar position, demonstrating that a single recombination event occurred prior to the divergence of these two strains.
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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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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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Volobueva, Alexandrina S., Tatyana G. Fedorchenko, Galina N. Lipunova, Marina S. Valova, Valeriya A. Sbarzaglia, Anna S. Gladkikh, Olga I. Kanaeva, Natalia A. Tolstykh, Andrey N. Gorshkov, and Vladimir V. Zarubaev. "Leucoverdazyls as Novel Potent Inhibitors of Enterovirus Replication." Pathogens 13, no. 5 (May 15, 2024): 410. http://dx.doi.org/10.3390/pathogens13050410.

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Enteroviruses (EV) are important pathogens causing human disease with various clinical manifestations. To date, treatment of enteroviral infections is mainly supportive since no vaccination or antiviral drugs are approved for their prevention or treatment. Here, we describe the antiviral properties and mechanisms of action of leucoverdazyls—novel heterocyclic compounds with antioxidant potential. The lead compound, 1a, demonstrated low cytotoxicity along with high antioxidant and virus-inhibiting activity. A viral strain resistant to 1a was selected, and the development of resistance was shown to be accompanied by mutation of virus-specific non-structural protein 2C. This resistant virus had lower fitness when grown in cell culture. Taken together, our results demonstrate high antiviral potential of leucoverdazyls as novel inhibitors of enterovirus replication and support previous evidence of an important role of 2C proteins in EV replication.
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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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