An Update on Enterovirus Research

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (31 October 2024) | Viewed by 25488

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Guest Editor
Departments of Pathology, Pediatrics, and Microbiology, Immunology & Tropical Medicine, George Washington University School of Medicine and Health Sciences, Children's National Hospital, Washington, DC, USA
Interests: hepatitis viruses; poxviruses; coronaviruses; arboviruses; enterovirus; influenza; clinical and diagnostic virology; virus-host interactions; antiviral development
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Dear Colleagues,

Enteroviruses belong to the family Picornaviridae and consist of 15 species, among which enteroviruses A through D cause infections in humans. Human enteroviruses are responsible for a broad array of diseases ranging from mild respiratory illness and hand, foot, and mouth disease to aseptic meningitis and acute flaccid paralysis. Most school-aged children have serologic evidence of prior infection. Human enteroviruses spread via the fecal–oral and respiratory routes and cause GI or respiratory illness. Viral invasion into the central nervous system, especially in neonates, can cause meningitis, encephalitis, seizures, brain imaging abnormalities, and long-term neurodevelopmental sequelae.

Despite the significant global burden of enterovirus infections, there are no approved antiviral agents available for the therapy of enterovirus infections. There are a variety of challenges in the implementation, utilization, and interpretation of novel diagnostic assays for the detection of enteroviral infections in a clinical setting. There are also multiple knowledge gaps in the field of enterovirus research, such as enterovirus life cycle, viral evolution, and virus–host interactions. Considering the clinical significance and global impact of enterovirus infections, efforts to push enterovirus research forward are urgently needed, and this field is attracting increasing attention worldwide. This Special Issue of Viruses aims to highlight the recent progress in research on enteroviruses.

Dr. Benjamin Liu
Guest Editor

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Keywords

  • antivirals
  • enteroviruses
  • picornavirus
  • diagnostics
  • emerging and re-emerging diseases
  • viral proteins
  • virus replication
  • viral targets
  • virus–host interactions
  • vaccine development

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Published Papers (15 papers)

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Research

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18 pages, 2694 KiB  
Article
Common Chemical Plasticizer Di(2-Ethhylhexyl) Phthalate Exposure Exacerbates Coxsackievirus B3 Infection
by Ramina Kordbacheh, Madelyn Ashley, William D. Cutts, Taryn E. Keyzer, Shruti Chatterjee, Tyler J. Altman, Natalie G. Alexander, Timothy E. Sparer, Brandon J. Kim and Jon Sin
Viruses 2024, 16(12), 1821; https://doi.org/10.3390/v16121821 - 23 Nov 2024
Viewed by 1123
Abstract
Di(2-ethhylhexyl) phthalate (DEHP) is a common plastic rubberizer. DEHP leaches from plastic matrices and is under increasing scrutiny as numerous studies have linked it to negative human health manifestations. Coxsackievirus B3 (CVB) is a human pathogen that typically causes subclinical infections but can [...] Read more.
Di(2-ethhylhexyl) phthalate (DEHP) is a common plastic rubberizer. DEHP leaches from plastic matrices and is under increasing scrutiny as numerous studies have linked it to negative human health manifestations. Coxsackievirus B3 (CVB) is a human pathogen that typically causes subclinical infections but can sometimes cause severe diseases such as pancreatitis, myocarditis, and meningoencephalitis. Though CVB infections are common, severe illness is relatively rare, and it is unclear what factors mediate disease severity. In this study, we sought to determine the effects that DEHP has on CVB infection in a variety of human cell types to evaluate whether this plastic-derived pollutant could represent a proviral environmental factor. Methods: HeLa cervical cancer cells, human induced pluripotent stem cell-derived brain-like endothelial cells (iBECs), and Caco-2 colon carcinoma cells were exposed to 40 µg/mL DEHP for 24 h prior to infecting with enhanced green fluorescent protein (EGFP)-expressing CVB. The severity of the infection was evaluated via fluorescence microscopy and flow cytometry-based viral EGFP detection, viral plaque assay on tissue culture media, and Western blotting to detect VP1 viral capsid protein. Interferon-associated proteins such as interferon regulatory factor (IRF) 3, IRF7, interferon-induced transmembrane (IFITM) 2, and IFITM3 were measured by Western blotting. The roles of IFITM2 and IFITM3 in the context of CVB infection were evaluated via siRNA silencing. Results: We found that DEHP drastically increased CVB infection in each of the cell types we tested, and, while the cellular processes underlying DEHP’s proviral properties were not entirely clear, we observed that DEHP may subvert CVB-induced interferon signaling and elevate levels of IFITMs, which appeared to bolster CVB infection. Conclusions: DEHP may represent a major environmental factor associated with the severity of CVB infection. Further understanding of how DEHP exacerbates infection may better elucidate its potential role as a proviral environmental factor. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research)
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16 pages, 3465 KiB  
Article
Recent Molecular Epidemiology of Echovirus 11 Throughout North and West Africa Resulted in the First Identification of a Recombinant Strain from an Acute Flaccid Paralysis Case in West Africa
by Ndack Ndiaye, Fatou Diène Thiaw, Adamou Lagare, Thérèse Sinare, Mohamed Lemine Diakité, Serigne Fallou Mbacké Ngom, Ousmane Kébé, Issifi Kollo Abdoulkader, Gassim Cissé, Mohamed Dia, Hermann Nodji Djimadoum, Christelle Ouedraogo Neya, Rakia Boubakar, Issaka Ouedraogo, Landoh Dadja Essoya, Ndongo Dia, Amadou Alpha Sall, Ousmane Faye and Martin Faye
Viruses 2024, 16(11), 1772; https://doi.org/10.3390/v16111772 - 13 Nov 2024
Viewed by 1273
Abstract
Echovirus 11 has emerged as a major public health concern, causing sepsis in neonates in many European countries in recent years. In Africa, especially West Africa, where resources and diagnostic capacities are limited, only sporadic cases have been reported. To better understand the [...] Read more.
Echovirus 11 has emerged as a major public health concern, causing sepsis in neonates in many European countries in recent years. In Africa, especially West Africa, where resources and diagnostic capacities are limited, only sporadic cases have been reported. To better understand the recent molecular epidemiology of E11 in West Africa, we characterized twenty-three echovirus 11 strains isolated through the acute flaccid paralysis and environmental surveillance systems for polio from 2013 to 2023, using high-throughput sequencing. Our data are noteworthy due to identifying for the first time a recombinant strain from an acute flaccid paralysis case and represent the first focus to date on molecular characterization of echovirus 11 in West Africa. Moreover, our data show that echovirus 11 diverged from 1970 (95% HPD range, 1961–1979) and evolved into four distinct clades, with the virus spread from West Africa to Europe, exhibiting two introductions in France around 2017, from Senegal and Guinea. Furthermore, the in silico analysis reveals four non-conservative amino acid substitutions in the VP1 sequences of the European strains associated with neonatal sepsis in newborns and a conserved amino acid motif in the VP1 protein toward enterovirus genotypes. Our data provide new insights into the epidemiology of echovirus 11 and point to the crucial need to implement specific surveillance programs targeting non-polio enteroviruses for the rapid identification of emerging or re-emerging enterovirus species, particularly in Africa. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research)
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14 pages, 3502 KiB  
Article
Phylodynamic and Epistatic Analysis of Coxsackievirus A24 and Its Variant
by Chia-Chi Cheng, Pei-Huan Chu, Hui-Wen Huang, Guan-Ming Ke, Liang-Yin Ke and Pei-Yu Chu
Viruses 2024, 16(8), 1267; https://doi.org/10.3390/v16081267 - 8 Aug 2024
Viewed by 1372
Abstract
Coxsackievirus A24 (CV-A24) is a human enterovirus that causes acute flaccid paralysis. However, a Coxsackievirus A24 variant (CV-A24v) is the most common cause of eye infections. The causes of these variable pathogenicity and tissue tropism remain unclear. To elucidate the phylodynamics of CV-A24 [...] Read more.
Coxsackievirus A24 (CV-A24) is a human enterovirus that causes acute flaccid paralysis. However, a Coxsackievirus A24 variant (CV-A24v) is the most common cause of eye infections. The causes of these variable pathogenicity and tissue tropism remain unclear. To elucidate the phylodynamics of CV-A24 and CV-A24v, we analyzed a dataset of 66 strains using Bayesian phylodynamic approach, along with detailed sequence variation and epistatic analyses. Six CV-A24 strains available in GenBank and 60 CV-A24v strains, including 11 Taiwanese strains, were included in this study. The results revealed striking differences between CV-A24 and CV-A24v exhibiting long terminal branches in the phylogenetic tree, respectively. CV-A24v presented distinct ladder-like clustering, indicating immune escape mechanisms. Notably, 10 genetic recombination events in the 3D regions were identified. Furthermore, 11 missense mutation signatures were detected to differentiate CV-A24 and CV-A24v; among these mutations, the F810Y substitution may significantly affect the secondary structure of the GH loop of VP1 and subsequently affect the epitopes of the capsid proteins. In conclusion, this study provides critical insights into the evolutionary dynamics and epidemiological characteristics of CV-A24 and CV-A24v, and highlights the differences in viral evolution and tissue tropism. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research)
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16 pages, 2366 KiB  
Article
Intensified Circulation of Echovirus 11 after the COVID-19 Pandemic in Poland: Detection of a Highly Pathogenic Virus Variant
by Beata Gad, Paulina Kłosiewicz, Kinga Oleksiak, Arleta Krzysztoszek, Kacper Toczyłowski, Artur Sulik, Tobiasz Wieczorek and Magdalena Wieczorek
Viruses 2024, 16(7), 1011; https://doi.org/10.3390/v16071011 - 24 Jun 2024
Cited by 1 | Viewed by 1754
Abstract
After the first phase of the COVID-19 pandemic in Europe, a new highly pathogenic variant of echovirus 11 (E11) was detected. The aim of this study was to analyze the genetic diversity of Polish E11 environmental and clinical strains circulating between 2017 and [...] Read more.
After the first phase of the COVID-19 pandemic in Europe, a new highly pathogenic variant of echovirus 11 (E11) was detected. The aim of this study was to analyze the genetic diversity of Polish E11 environmental and clinical strains circulating between 2017 and 2023 as well as compare them with E11 strains isolated from severe neonatal sepsis cases reported in Europe between 2022 and 2023. Additionally, the study explores the effectiveness of environmental monitoring in tracking the spread of new variants. For this purpose, the complete sequences of the VP1 capsid protein gene were determined for 266 E11 strains isolated in Poland from 2017 to 2023, and phylogenetic analysis was performed. In the years 2017–2023, a significant increase in the detection of E11 strains was observed in both environmental and clinical samples in Poland. The Polish E11 strains represented three different genotypes, C3, D5 and E, and were characterized by a high diversity. In Poland, the intensive circulation of the new variant E11, responsible for severe neonatal infections with a high mortality in Europe, was detected in the years 2022–2023. This investigation demonstrates the important role of environmental surveillance in the tracking of enteroviruses circulation, especially in settings with limited clinical surveillance. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research)
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24 pages, 4393 KiB  
Article
Exploration of Potential Broad-Spectrum Antiviral Targets in the Enterovirus Replication Element: Identification of Six Distinct 5′ Cloverleaves
by Morgan G. Daniels, Meagan E. Werner, Rockwell T. Li and Steven M. Pascal
Viruses 2024, 16(7), 1009; https://doi.org/10.3390/v16071009 - 23 Jun 2024
Viewed by 1240
Abstract
Enterovirus genomic replication initiates at a predicted RNA cloverleaf (5′CL) at the 5′ end of the RNA genome. The 5′CL contains one stem (SA) and three stem-loops (SLB, SLC, SLD). Here, we present an analysis of 5′CL conservation and divergence for 209 human [...] Read more.
Enterovirus genomic replication initiates at a predicted RNA cloverleaf (5′CL) at the 5′ end of the RNA genome. The 5′CL contains one stem (SA) and three stem-loops (SLB, SLC, SLD). Here, we present an analysis of 5′CL conservation and divergence for 209 human health-related serotypes from the enterovirus genus, including enterovirus and rhinovirus species. Phylogenetic analysis indicates six distinct 5′CL serotypes that only partially correlate with the species definition. Additional findings include that 5′CL sequence conservation is higher between the EV species than between the RV species, the 5′CL of EVA and EVB are nearly identical, and RVC has the lowest 5′CL conservation. Regions of high conservation throughout all species include SA and the loop and nearby bases of SLB, which is consistent with known protein interactions at these sites. In addition to the known protein binding site for the Poly-C binding protein in the loop of SLB, other conserved consecutive cytosines in the stems of SLB and SLC provide additional potential interaction sites that have not yet been explored. Other sites of conservation, including the predicted bulge of SLD and other conserved stem, loop, and junction regions, are more difficult to explain and suggest additional interactions or structural requirements that are not yet fully understood. This more intricate understanding of sequence and structure conservation and variability in the 5′CL may assist in the development of broad-spectrum antivirals against a wide range of enteroviruses, while better defining the range of virus isotypes expected to be affected by a particular antiviral. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research)
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14 pages, 2190 KiB  
Article
Application of MPBT Assay for Multiplex Determination of Infectious Titers and for Selection of the Optimal Formulation for the Trivalent Novel Oral Poliovirus Vaccine
by Hasmik Manukyan, Manjari Lal, Changcheng Zhu, Olga Singh, Tsai-Lien Lin, Erman Tritama, Konstantin Chumakov, Shwu-Maan Lee and Majid Laassri
Viruses 2024, 16(6), 961; https://doi.org/10.3390/v16060961 - 14 Jun 2024
Cited by 1 | Viewed by 1140
Abstract
Recently, a multiplex PCR-based titration (MPBT) assay was developed for simultaneous determination of infectious titers of all three Sabin strains of the oral poliovirus vaccine (OPV) to replace the conventional CCID50 assay, which is both time-consuming and laborious. The MPBT assay was [...] Read more.
Recently, a multiplex PCR-based titration (MPBT) assay was developed for simultaneous determination of infectious titers of all three Sabin strains of the oral poliovirus vaccine (OPV) to replace the conventional CCID50 assay, which is both time-consuming and laborious. The MPBT assay was shown to be reproducible, robust and sensitive. The conventional and MPBT assays showed similar results and sensitivity. The MPBT assay can be completed in two to three days, instead of ten days for the conventional assay. To prevent attenuated vaccine strains of poliovirus from reversion to virulence, a novel, genetically stable OPV (nOPV) was developed by modifying the genomes of conventional Sabin strains used in OPV. In this work, we evaluated the MPBT assay as a rapid screening tool to support trivalent nOPV (tnOPV) formulation development by simultaneous titration of the three nOPV strains to confirm stability as needed, for the selection of the lead tnOPV formulation candidate. We first assessed the ability of the MPBT assay to discriminate a 0.5 log10 titer difference by titrating the two tnOPV samples (undiluted and threefold-diluted) on the same plate. Once the assay was shown to be discriminating, we then tested different formulations of tnOPV drug products (DPs) that were subjected to different exposure times at 37 °C (untreated group and treated groups: 2 and 7 days at 37 °C), and to three freeze and thaw (FT) cycles. Final confirmation of the down selected formulation candidates was achieved by performing the conventional CCID50 assay, comparing the stability of untreated and treated groups and FT stability testing on the top three candidates. The results showed that the MPBT assay generates similar titers as the conventional assay. By testing two trivalent samples in the same plate, the assay can differentiate a 0.5 log10 difference between the titers of the tested nOPV samples. Also, the assay was able to detect the gradual degradation of nOPV viruses with different formulation compositions and under different time/temperature conditions and freeze/thaw cycles. We found that there were three tnOPV formulations which met the stability criteria of less than 0.5 log10 loss after 2 days’ exposure to 37 ℃ and after three FT cycles, maintaining the potency of all three serotypes in these formulations. The ability of the MPBT assay to titrate two tnOPV lots (six viruses) in the same plate makes it cheaper and gives it a higher throughput for rapid screening. The assay detected the gradual degradation of the tnOPV and was successful in the selection of optimal formulations for the tnOPV. The results demonstrated that the MPBT method can be used as a stability indicating assay to assess the thermal stability of the nOPV. It can be used for rapid virus titer determination during the vaccine manufacturing process, and in clinical trials. The MPBT assay can be automated and applied for other viruses, including those with no cytopathic effect. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research)
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11 pages, 2426 KiB  
Article
Caboxamycin Inhibits Heart Inflammation in a Coxsackievirus B3-Induced Myocarditis Mouse Model
by Hong-Gi Kim, Prima F. Hillman, You-Jeung Lee, Ha-Eun Jeon, Byung-Kwan Lim and Sang-Jip Nam
Viruses 2024, 16(5), 677; https://doi.org/10.3390/v16050677 - 25 Apr 2024
Cited by 1 | Viewed by 1595
Abstract
Coxsackievirus B3 (CVB3) is a positive single-strand RNA genome virus which belongs to the enterovirus genus in the picornavirus family, like poliovirus. It is one of the most prevalent pathogens that cause myocarditis and pancreatitis in humans. However, a suitable therapeutic medication and [...] Read more.
Coxsackievirus B3 (CVB3) is a positive single-strand RNA genome virus which belongs to the enterovirus genus in the picornavirus family, like poliovirus. It is one of the most prevalent pathogens that cause myocarditis and pancreatitis in humans. However, a suitable therapeutic medication and vaccination have yet to be discovered. Caboxamycin, a benzoxazole antibiotic isolated from the culture broth of the marine strain Streptomyces sp., SC0774, showed an antiviral effect in CVB3-infected HeLa cells and a CVB3-induced myocarditis mouse model. Caboxamycin substantially decreased CVB3 VP1 production and cleavage of translation factor eIF4G1 from CVB3 infection. Virus-positive and -negative strand RNA was dramatically reduced by caboxamycin treatment. In addition, the cleavage of the pro-apoptotic molecules BAD, BAX, and caspase3 was significantly inhibited by caboxamycin treatment. In animal experiments, the survival rate of mice was improved following caboxamycin treatment. Moreover, caboxamycin treatment significantly decreased myocardial damage and inflammatory cell infiltration. Our study showed that caboxamycin dramatically suppressed cardiac inflammation and mouse death. This result suggests that caboxamycin may be suitable as a potential antiviral drug for CVB3. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research)
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11 pages, 1985 KiB  
Article
Quantitation of Enterovirus A71 Empty and Full Particles by Sedimentation Velocity Analytical Ultracentrifugation
by Anna Yang, Yun Luo, Jie Yang, Tingbo Xie, Wenhui Wang, Xin Wan, Kaiwen Wang, Deqin Pang, Dongsheng Yang, Hanyu Dai, Jie Wu, Shengli Meng, Jing Guo, Zejun Wang and Shuo Shen
Viruses 2024, 16(4), 573; https://doi.org/10.3390/v16040573 - 8 Apr 2024
Cited by 1 | Viewed by 1628
Abstract
The enterovirus A71 (EV71) inactivated vaccine is an effective intervention to control the spread of the virus and prevent EV71-associated hand, foot, and mouth disease (HFMD). It is widely administered to infants and children in China. The empty particles (EPs) and full particles [...] Read more.
The enterovirus A71 (EV71) inactivated vaccine is an effective intervention to control the spread of the virus and prevent EV71-associated hand, foot, and mouth disease (HFMD). It is widely administered to infants and children in China. The empty particles (EPs) and full particles (FPs) generated during production have different antigenic and immunogenic properties. However, the antigen detection methods currently used were established without considering the differences in antigenicity between EPs and FPs. There is also a lack of other effective analytical methods for detecting the different particle forms, which hinders the consistency between batches of products. In this study, we analyzed the application of sedimentation velocity analytical ultracentrifugation (SV-AUC) in characterizing the EPs and FPs of EV71. Our results showed that the proportions of the two forms could be quantified simultaneously by SV-AUC. We also determined the repeatability and accuracy of this method and found that both parameters were satisfactory. We assessed SV-AUC for bulk vaccine quality control, and our findings indicated that SV-AUC can be used effectively to analyze the percentage of EPs and FPs and monitor the consistency of the process to ensure the quality of the vaccine. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research)
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9 pages, 912 KiB  
Communication
Epidemiological and Genetic Characterization of Coxsackievirus A6-Associated Hand, Foot, and Mouth Disease in Gwangju, South Korea, in 2022
by Ji-Eun Lee, Min-Ji Kim, Mi-Hyeon Lim, Sue-Ji Han, Jin-Yeong Kim, Soo-Hoo Kim, Yi-Duen Ha, Gyung-Li Gang, Yoon-Seok Chung and Jung-Mi Seo
Viruses 2024, 16(3), 476; https://doi.org/10.3390/v16030476 - 20 Mar 2024
Viewed by 2723
Abstract
Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When [...] Read more.
Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When social mitigation was relaxed during the COVID-19 pandemic in 2022, the re-emergence of HFMD was observed in Gwangju, South Korea, and seasonal characteristics of the disease appeared to have changed. To investigate the molecular characteristics of enterovirus (EV) associated with HFMD during 2022, 277 specimens were collected. Children aged younger than 5 years accounted for the majority of affected individuals. EV detection and genotyping were performed using real-time RT-PCR and nested RT-PCR followed by sequence analysis. The EV detection rate was found to be 82.3%, and the main genotype identified was CV-A6. Sixteen CV-A6 samples were selected for whole genome sequencing. According to phylogenetic analysis, all CV-A6 strains from this study belonged to the sub-genotype D3 clade based on VP1 sequences. Analysis of 3D polymerase phylogeny showed that only the recombinant RF-A group was identified. In conclusion, circulating EV types should be continuously monitored to understand pathogen emergence and evolution during the post-pandemic era. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research)
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14 pages, 689 KiB  
Article
Investigation of the Correlation between Enterovirus Infection and the Climate Factor Complex Including the Ping-Year Factor and El Niño-Southern Oscillation in Taiwan
by Hsueh-Wen Yu, Chia-Hsuan Kuan, Liang-Wei Tseng, Hsing-Yu Chen, Meg-Yen Tsai and Yu-Sheng Chen
Viruses 2024, 16(3), 471; https://doi.org/10.3390/v16030471 - 20 Mar 2024
Cited by 3 | Viewed by 1820
Abstract
Enterovirus infection and enterovirus infection with severe complications (EVSC) are critical issues in several aspects. However, there is no suitable predictive tool for these infections. A climate factor complex (CFC) containing several climate factors could provide more effective predictions. The ping-year factor (PYF) [...] Read more.
Enterovirus infection and enterovirus infection with severe complications (EVSC) are critical issues in several aspects. However, there is no suitable predictive tool for these infections. A climate factor complex (CFC) containing several climate factors could provide more effective predictions. The ping-year factor (PYF) and El Niño-Southern Oscillation (ENSO) are possible CFCs. This study aimed to determine the relationship between these two CFCs and the incidence of enterovirus infection. Children aged 15 years and younger with enterovirus infection and/or EVSC were enrolled between 2007 and 2022. Each year was categorized into a ping-year or non-ping-year according to the PYF. Poisson regression was used to evaluate the associations between the PYF, ENSO, and the incidence of enterovirus infection. Compared to the ping-year group, the incidence rate of enterovirus infection, the incidence rate of EVSC, and the ratio of EVSC in the non-ping-year group were 1.24, 3.38, and 2.73 times higher, respectively (p < 0.001). For every one-unit increase in La Niña, the incidence rate of enterovirus infection decreased to 0.96 times (p < 0.001). Our study indicated that CFCs could be potential predictors for enterovirus infection, and the PYF was more suitable than ENSO. Further research is needed to improve the predictive model. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research)
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20 pages, 4411 KiB  
Article
Cordycepin Inhibits Enterovirus A71 Replication and Protects Host Cell from Virus-Induced Cytotoxicity through Adenosine Action Pathway
by Yi-Ping Lee, Chun-Keung Yu, Tak-Wah Wong, Li-Ching Chen and Bu-Miin Huang
Viruses 2024, 16(3), 352; https://doi.org/10.3390/v16030352 - 24 Feb 2024
Cited by 1 | Viewed by 1761
Abstract
Enterovirus A71 (EV-A71) infection typically causes mild illnesses, such as hand-foot-and-mouth disease (HFMD), but occasionally leads to severe or fatal neurological complications in infants and young children. Currently, there is no specific antiviral treatment available for EV-A71 infection. Thus, the development of an [...] Read more.
Enterovirus A71 (EV-A71) infection typically causes mild illnesses, such as hand-foot-and-mouth disease (HFMD), but occasionally leads to severe or fatal neurological complications in infants and young children. Currently, there is no specific antiviral treatment available for EV-A71 infection. Thus, the development of an effective anti-EV-A71 drug is required urgently. Cordycepin, a major bioactive compound found in Cordyceps fungus, has been reported to possess antiviral activity. However, its specific activity against EV-A71 is unknown. In this study, the potency and role of cordycepin treatment on EV-A71 infection were investigated. Results demonstrated that cordycepin treatment significantly reduced the viral load and viral ribonucleic acid (RNA) level in EV-A71-infected Vero cells. In addition, EV-A71-mediated cytotoxicity was significantly inhibited in the presence of cordycepin in a dose-dependent manner. The protective effect can also be extended to Caco-2 intestinal cells, as evidenced by the higher median tissue culture infectious dose (TCID50) values in the cordycepin-treated groups. Furthermore, cordycepin inhibited EV-A71 replication by acting on the adenosine pathway at the post-infection stage. Taken together, our findings reveal that cordycepin could be a potential antiviral candidate for the treatment of EV-A71 infection. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research)
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14 pages, 10714 KiB  
Article
Molecular Amplification and Cell Culturing Efficiency for Enteroviruses’ Detection in Cerebrospinal Fluids of Algerian Patients Suffering from Meningitis
by Abdelwahab Rai, Zohra Ammi, Dahbia Leila Anes-Boulahbal, Aymen Amin Assadi, Abdeltif Amrane, Oussama Baaloudj and Lotfi Mouni
Viruses 2024, 16(2), 170; https://doi.org/10.3390/v16020170 - 23 Jan 2024
Cited by 1 | Viewed by 1798
Abstract
Enteroviruses (EVs) represent a major cause of viral meningitis, being responsible for nearly 1 billion infections each year worldwide. Several techniques were developed to obtain better diagnostic results of EV infections. Herein, we evaluated the efficiency of EV detection through isolation on both [...] Read more.
Enteroviruses (EVs) represent a major cause of viral meningitis, being responsible for nearly 1 billion infections each year worldwide. Several techniques were developed to obtain better diagnostic results of EV infections. Herein, we evaluated the efficiency of EV detection through isolation on both Rhabdomyosarcoma (RD) and Vero cell line cultures, conventional reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR. Thus, 50 cerebrospinal fluid (CSF) samples belonging to patients suspected to have viral meningitis in northern Algeria were collected, anonymously numbered from 1 to 50 and subjected to the above-mentioned techniques for EV detection. Using real-time RT-PCR, 34 CSF samples were revealed to be positive for viral origin of meningitis (68%). Thirteen of them were positive when the conventional RT-PCR was used (26%), and only three samples gave positive results when the cell culture technique was used (6%). Surprisingly, two cell culture-positive CSF samples, namely, 31 and 39, were negative using RT-PCR directly on the original samples. However, they turned to be positive when amplification was carried out on their corresponding cell culture supernatant. The cell-cultured viral isolates were then identified by sequencing their viral genome’s VP1 regions. All of them were revealed to belong to the echovirus 27 strain. This investigation demonstrates that RT-PCR techniques are often more sensitive, accurate and much faster, providing reliable results within a clinically acceptable timeframe. However, viral isolation on cell cultures remains crucial to obtain enough viral load for serological tests or even to avoid the rare, but existing, false negative PCR. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research)
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12 pages, 1073 KiB  
Review
An Overview of the Characteristics, Pathogenesis, Epidemiology, and Detection of Human Enterovirus in the Arabian Gulf Region
by Mohammed Ayyub, Joshua George Thomas and Rawad Hodeify
Viruses 2024, 16(8), 1187; https://doi.org/10.3390/v16081187 - 24 Jul 2024
Viewed by 1427
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research)
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16 pages, 595 KiB  
Review
Epidemiology of Enterovirus Genotypes in Association with Human Diseases
by Zhenfeng Xie, Pattara Khamrin, Niwat Maneekarn and Kattareeya Kumthip
Viruses 2024, 16(7), 1165; https://doi.org/10.3390/v16071165 - 19 Jul 2024
Cited by 5 | Viewed by 1998
Abstract
Enteroviruses (EVs) are well-known causes of a wide range of infectious diseases in infants and young children, ranging from mild illnesses to severe conditions, depending on the virus genotypes and the host’s immunity. Recent advances in molecular surveillance and genotyping tools have identified [...] Read more.
Enteroviruses (EVs) are well-known causes of a wide range of infectious diseases in infants and young children, ranging from mild illnesses to severe conditions, depending on the virus genotypes and the host’s immunity. Recent advances in molecular surveillance and genotyping tools have identified over 116 different human EV genotypes from various types of clinical samples. However, the current knowledge about most of these genotypes, except for those of well-known genotypes like EV-A71 and EV-D68, is still limited due to a lack of comprehensive EV surveillance systems. This limited information makes it difficult to understand the true burden of EV-related diseases globally. Furthermore, the specific EV genotype associated with diseases varies according to country, population group, and study period. The same genotype can exhibit different epidemiological features in different areas. By integrating the data from established EV surveillance systems in the USA, Europe, Japan, and China, in combination with other EV infection studies, we can elaborate a better understanding of the distribution of prevalent EV genotypes and the diseases associated with EV. This review analyzed the data from various EV surveillance databases and explored the EV seroprevalence and the association of specific EV genotypes with human diseases. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research)
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8 pages, 1845 KiB  
Brief Report
Unveiling of the Co-Infection of Peste des Petits Ruminants Virus and Caprine Enterovirus in Goat Herds with Severe Diarrhea in China
by Qun Zhang, Xuebo Zheng, Fan Zhang, Xuyuan Cui, Naitian Yan, Junying Hu, Yidi Guo and Xinping Wang
Viruses 2024, 16(6), 986; https://doi.org/10.3390/v16060986 - 19 Jun 2024
Cited by 3 | Viewed by 1123
Abstract
Here, we report the discovery of two viruses associated with a disease characterized by severe diarrhea on a large-scale goat farm in Jilin province. Electron Microscopy observations revealed two kinds of virus particles with the sizes of 150–210 nm and 20–30 nm, respectively. [...] Read more.
Here, we report the discovery of two viruses associated with a disease characterized by severe diarrhea on a large-scale goat farm in Jilin province. Electron Microscopy observations revealed two kinds of virus particles with the sizes of 150–210 nm and 20–30 nm, respectively. Detection of 276 fecal specimens from the diseased herds showed the extensive infection of peste des petits ruminants virus (63.77%, 176/276) and caprine enterovirus (76.81%, 212/276), with a co-infection rate of 57.97% (160/276). These results were partially validated with RT-PCR, where all five PPRV-positive and CEV-positive specimens yielded the expected size of fragments, respectively, while no fragments were amplified from PPRV-negative and CEV-negative specimens. Moreover, corresponding PPRV and CEV fragments were amplified in PPRV and CEV double-positive specimens. Histopathological examinations revealed severe microscopic lesions such as degeneration, necrosis, and detachment of epithelial cells in the bronchioles and intestine. An immunohistochemistry assay detected PPRV antigens in bronchioles, cartilage tissue, intestine, and lymph nodes. Simultaneously, caprine enterovirus antigens were detected in lung, kidney, and intestinal tissues from the goats infected by the peste des petits ruminants virus. These results demonstrated the co-infection of peste des petits ruminants virus with caprine enterovirus in goats, revealing the tissue tropism for these two viruses, thus laying a basis for the future diagnosis, prevention, and epidemiological survey for these two virus infections. Full article
(This article belongs to the Special Issue An Update on Enterovirus Research)
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