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: 30 June 2024 | Viewed by 4508

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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: poxviruses; coronaviruses; arboviruses; enterovirus; influenza; clinical and diagnostic virology; virus–host interactions; antiviral development; hepatitis viruses; parechovirus; antiviral drug resistance
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Special Issue Information

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

Published Papers (6 papers)

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Research

11 pages, 1192 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
Viewed by 217
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)
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 - 08 Apr 2024
Viewed by 459
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 871
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
Viewed by 760
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
Viewed by 715
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
Viewed by 988
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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