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Coxsackieviruses, Polioviruses and Associated Diseases (Second Edition)

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

Deadline for manuscript submissions: 1 May 2026 | Viewed by 7207

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Prof. Dr. Yong Zhang

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WHO WPRO Regional Polio Reference Laboratory, National Health Commission Key Laboratory for Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
Interests: human enterovirus disease; molecular evolution and epidemiology; coxsackieviruses
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Prof. Dr. Didier Hober

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Laboratoire de Virologie ULR3610, University of Lille, CHU Lille, 59000 Lille, France
Interests: enterovirus; coxsackieviruses; viral pathogenesis
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Dear Colleagues,

Coxsackieviruses (CVs), including groups A and B (Picornaviridae), are ubiquitous single-stranded RNA-positive human pathogens. Their ability to utilize various cell receptors explains their widespread tissue tropism and their incredibly diverse pathogenicity. CVs are associated with various human diseases, including but not limited to the following: 1. respiratory infection, manifested as cold symptoms, sore throat, cough, etc.; 2. hand, foot, and mouth disease and herpetic pharyngitis, as CVs are the main pathogens causing these diseases, common in children and presenting symptoms such as oral ulcers and herpes on the hands and feet; 3. encephalitis (meningitis), as CV infection can also lead to encephalomyelitis, manifested as severe neurological complications such as meningitis, encephalitis, and myelitis; 4. myocarditis, which can sometimes be caused by CV infection, leading to impaired heart function and heart inflammation; 5. other diseases, such as muscle weakness, acute flaccid paralysis, etc.

Their great capacity for genetic evolution has made them pathogens with a high potential for emergence. These viruses can modulate the innate defense mechanisms of the target cell, as well as the functionality of immune system cells, promoting immune system evasion. Currently, the mechanisms underlying CVs’ genetic evolution and modulation of inflammatory and immune responses remain to be explored, and their elucidation is critical for the development of future therapeutic or vaccine strategies, helping to prevent and treat related diseases.

Polioviruses, on the other hand, are the causative agents of poliomyelitis, a debilitating and sometimes fatal disease which has been the target of global eradication efforts. The development of effective vaccines in the mid-20th century was a landmark achievement in public health, leading to the near-eradication of wild-type poliovirus. However, the emergence of vaccine-derived poliovirus (VDPV) outbreaks in under-immunized populations highlights the need for continued research and vigilance.

This Special Issue aims to provide a comprehensive overview of the current state of research on coxsackieviruses, polioviruses, and their associated diseases. Original research articles, review articles, and perspective pieces covering a wide range of topics, including virus evolution, host–pathogen interactions, diagnostic methods, and the development of novel therapeutic and preventive strategies, are welcome. By addressing these important and timely issues, this Special Issue will serve as a valuable resource for researchers, clinicians, and public health professionals working in the field of picornavirus research and disease management.

Prof. Dr. Yong Zhang
Prof. Dr. Didier Hober
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

coxsackievirus
HFMD
viral Meningitis
myocarditis
pericarditis
herpangina
poliovirus
poliomyelitis
acute flaccid paralysis
post-polio syndrome
pleurodynia (Bornholm disease)

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Coxsackieviruses and Associated Diseases in Viruses (9 articles)

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Research

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18 pages, 5404 KiB

Open AccessArticle

Evolutionary Studies on the Coxsackievirus A-24 Variants Causing Acute Hemorrhagic Conjunctivitis with Emphasis on the Recent Outbreak of 2023 in India

by Sanjaykumar Tikute, Jahnabee Boro, Vikas Sharma, Anita Shete, Alfia Fathima Ashraf, Ranjana Mariyam Raju, Sarah Cherian and Mallika Lavania

Viruses 2025, 17(3), 371; https://doi.org/10.3390/v17030371 - 5 Mar 2025

Viewed by 744

Abstract

Acute Hemorrhagic Conjunctivitis (AHC) is primarily caused by viral infections, with Coxsackievirus A-24v (CV-A24v) being a significant culprit. Enteroviruses, including CV-A24v, are responsible for global AHC outbreaks. Over time, CV-A24v has evolved, and genotype IV (GIV) has become the dominant strain. This study focused on examining the genetic features and evolutionary trends of CV-A24v responsible for the recent AHC outbreak of 2023 in India. Researchers isolated viral strains from ocular swabs and confirmed the presence of CV-A24v using reverse transcriptase quantitative PCR (RT-qPCR) and whole-genome sequencing. Genomic comparisons between isolates of 2023 and those from a previous outbreak in 2009 were conducted. Phylogenetic analysis revealed that the 2023 isolates formed a distinct cluster within GIV-5 and were related to recent strains from China and Pakistan. The older Indian isolates from 2009 grouped with GIV-3. New subclades, GIV-6 and GIV-7, were also identified in this study, indicating the diversification of CV-A24. Molecular clock and phylogeographic analysis traced the virus’s circulation back to the 1960s, with the common ancestor likely to have originated in Singapore in 1968. The 2023 Indian strains probably originated from Thailand around 2014, with subsequent spread to China and Pakistan. This study concluded that the 2023 outbreak was caused by a genetically distinct CV-A24v strain with nine mutations, underlining the virus’s ongoing evolution and adaptations and offering valuable insights for future outbreak control. Full article

(This article belongs to the Special Issue Coxsackieviruses, Polioviruses and Associated Diseases (Second Edition))

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12 pages, 1652 KiB

Open AccessArticle

Seroprevalence of Enterovirus 71 Among Children in Western India

by Madhu Chhanda Mohanty, Swapnil Y. Varose, Sneha V. Rane, Shailesh D. Pawar and Babasaheb V. Tandale

Viruses 2025, 17(3), 356; https://doi.org/10.3390/v17030356 - 28 Feb 2025

Viewed by 453

Abstract

Hand-foot-and-mouth disease (HFMD) caused by Enterovirus 71 (EV71) is highly infectious and can lead to serious neurological complications. This study proposed to evaluate the seroprevalence of EV71 in children of two states of western India by estimating neutralizing antibodies (nAbs) to EV71 genotypes D, G, and C isolated in India, using micro-neutralization assay. Among the serum samples of 612 children tested, 213 (34.80%, 95% CI: 31.00–38.73) and 312 (51.00%, 95% CI: 47.00–55.00) were positive for nAbs to EV71 BrCr and indigenous genotype D, respectively, with a significant rise with age for genotype D. However, compared to other age groups, only 23.2% of children aged 1–5 years showed nAbs to EV71 genotype D with a considerably lower Geometric Mean Titer, indicating the susceptibility of this age group to EV71 infection. Our study confirms the circulation of EV71 in India with relatively high susceptibility of children up to 5 years to EV71 infections. Full article

(This article belongs to the Special Issue Coxsackieviruses, Polioviruses and Associated Diseases (Second Edition))

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8 pages, 1188 KiB

Open AccessArticle

The Emergence of Coxsackievirus A16 Subgenotype B1c: A Key Driver of the Hand, Foot, and Mouth Disease Epidemic in Guangdong, China

by Huiling Zeng, Biao Zeng, Lina Yi, Lin Qu, Jiadian Cao, Fen Yang, Haiyi Yang, Chunyan Xie, Yuxi Yan, Wenwen Deng, Shuling Li, Yingtao Zhang, Baisheng Li, Jing Lu and Hanri Zeng

Viruses 2025, 17(2), 219; https://doi.org/10.3390/v17020219 - 3 Feb 2025

Viewed by 963

Abstract

Background: In 2024, mainland China witnessed a significant upsurge in Hand, Foot, and Mouth Disease (HFMD) cases. Coxsackievirus A16 (CVA16) is one of the primary causative agents of HFMD. Long-term monitoring of theCVA16 infection rate and genotype changes is crucial for the prevention and control of HFMD. Methods: A total of 40,673 clinical specimens were collected from suspected HFMD cases in Guangdong province from 2018 to 2024, including rectal swabs (n = 27,954), throat swabs (n = 6791), stool (n = 5923), cerebrospinal fluid (n = 3), and herpes fluid (n = 2). A total of 24,410 samples were detected as EV-positive and further typed by RT-PCR. A total of 872 CVA16-positive samples were isolated and further sequenced to obtain the full-length VP1 sequence. Phylogenetic analysis was performed based on viral protein 1 gene (VP1). Results: In the first 25 weeks of 2024, reported cases of HFMD were 1.36 times higher than the mean rates of 2023. In 2024, CVA16 predominated at 75.42%, contrasting with the past etiological pattern in which the CVA6 was predominant with the detection rate ranging from 32.85 to 77.61% from 2019 to 2023. Phylogenetic analysis based on the VP1 gene revealed that the B1a and B1b subtypes co-circulated in Guangdong from 2018 to 2022. The B1c outbreak clade, detected in Guangdong in 2023, constituted 68.24% of the 148 strains of CVA16 collected in 2024, suggesting a subtype shift in the CVA16 virus. There were three specific amino acid variations (P3S, I235V, and T240A) in the VP1 sequence of B1c. Conclusions: The new emergence of the CVA16 B1c outbreak clade in Guangdong during 2023–2024 highlights the necessity for the enhanced surveillance of the virus evolution epidemiological dynamic in this region. Furthermore, it is imperative to closely monitor the etiological pattern changes in Hand, Foot, and Mouth Disease (HFMD) in other regions as well. Such vigilance will be instrumental in guiding future vaccination strategies for HFMD. Full article

(This article belongs to the Special Issue Coxsackieviruses, Polioviruses and Associated Diseases (Second Edition))

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17 pages, 10291 KiB

Open AccessArticle

Screening of Insertion Sites and Tags on EV-A71 VP1 Protein for Recombinant Virus Construction

by Miaomiao Kang, Xiangyi Li, Xiaohong Li, Rui Yu, Shuo Zhang, Jingjing Yan, Xiaoyan Zhang, Jianqing Xu, Buyong Ma and Shuye Zhang

Viruses 2025, 17(1), 128; https://doi.org/10.3390/v17010128 - 17 Jan 2025

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Abstract

This study aimed to create a new recombinant virus by modifying the EV-A71 capsid protein, serving as a useful tool and model for studying human Enteroviruses. We developed a new screening method using EV-A71 pseudovirus particles to systematically identify suitable insertion sites and tag types in the VP1 capsid protein. The pseudovirus’s infectivity and replication can be assessed by measuring postinfection luciferase signals. We reported that the site after the 100th amino acid within the VP1 BC loop of EV-A71 is particularly permissive for the insertion of various tags. Notably, the introduction of S and V5 tags at this position had minimal effect on the fitness of the tagged pseudovirus. Furthermore, recombinant infectious EV-A71 strains tagged with S and V5 epitopes were successfully rescued, and the stability of these tags was verified. Computational analysis suggested that viable insertions should be compatible with capsid assembly and receptor binding, whereas non-viable insertions could potentially disrupt the capsid’s binding with heparan sulfate. We expect the tagged recombinant EV-A71 to be a useful tool for studying the various stages of the enterovirus life cycle and for virus purification, immunoprecipitation, and research in immunology and vaccine development. Furthermore, this study serves as a proof of principle and may help develop similar tags in enteroviruses, for which there are fewer available tools. Full article

(This article belongs to the Special Issue Coxsackieviruses, Polioviruses and Associated Diseases (Second Edition))

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14 pages, 1521 KiB

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Epidemiology of Hand, Foot, and Mouth Disease and Genetic Characterization of Coxsackievirus A16 in Shenyang, Liaoning Province, China, 2013–2023

by Fan Li, Qian Zhang, Jinbo Xiao, Huijie Chen, Shi Cong, Ling Chen, Huanhuan Lu, Shuangli Zhu, Tianjiao Ji, Qian Yang, Dongyan Wang, Dongmei Yan, Na Liu, Jichen Li, Yucai Liang, Lei Zhou, Mengyi Xiao, Yong Zhang and Baijun Sun

Viruses 2024, 16(11), 1666; https://doi.org/10.3390/v16111666 - 24 Oct 2024

Viewed by 1165

Abstract

Hand, foot, and mouth disease (HFMD), a common childhood infection caused by enterovirus, poses a serious public health concern in China. We collected and analyzed epidemiological data on 62,133 HFMD cases in Shenyang City, Liaoning Province, from 2013 to 2023. The average annual incidence was 76.12 per 100,000 person-years; 99.45% of cases were mild, while 0.55% were severe. Only one patient died. HFMD infections peaked annually in July. Children in kindergartens and scattered children accounted for 44.6% and 42.2% of cases, respectively. Real-time RT-PCR detection of enteroviruses in 5534 patient samples revealed 3780 positives, of which 25.1% were CVA16-positive. Positives were randomly sampled, yielding 240 VP1 sequences of CVA16. Phylogenetic tree results showed that all VP1 sequences belonged to the B1 sub-genogroup. However, the sub-genogroup prevalence varied over time: from 2013 to 2014 and 2019 to 2021, the predominant sub-genogroup was B1a, while it was B1b from 2015 to 2018. Further phylogenetic analyses showed substantial divergence between B1a branches in CVA16, suggesting possible turnover of the B1a sub-genogroup in CVA16 due to evolution. This study provides epidemiological data on HFMD in Shenyang, and provides a phylogenetic analysis of CVA16, offering a theoretical basis for preventing and controlling HFMD in Shenyang City. Full article

(This article belongs to the Special Issue Coxsackieviruses, Polioviruses and Associated Diseases (Second Edition))

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16 pages, 2806 KiB

Open AccessArticle

Coxsackievirus B3 Activates Macrophages Independently of CAR-Mediated Viral Entry

by Yasir Mohamud, Jingfei Carly Lin, Sinwoo Wendy Hwang, Amirhossein Bahreyni, Zhihan Claire Wang and Honglin Luo

Viruses 2024, 16(9), 1456; https://doi.org/10.3390/v16091456 - 13 Sep 2024

Cited by 2 | Viewed by 1567

Abstract

Enteroviruses are a genus of small RNA viruses that are responsible for approximately one billion global infections annually. These infections range in severity from the common cold and flu-like symptoms to more severe diseases, such as viral myocarditis, pancreatitis, and neurological disorders, that continue to pose a global health challenge with limited therapeutic strategies currently available. In the current study, we sought to understand the interaction between coxsackievirus B3 (CVB3), which is a model enterovirus, and macrophage cells, as there is limited understanding of how this virus interacts with macrophage innate immune cells. Our study demonstrated that CVB3 can robustly activate macrophages without apparent viral replication in these cells. We also showed that myeloid cells lacked the viral entry receptor coxsackievirus and adenovirus receptor (CAR). However, the expression of exogenous CAR in RAW264.7 macrophages was unable to overcome the viral replication deficit. Interestingly, the CAR expression was associated with altered inflammatory responses during prolonged infection. Additionally, we identified the autophagy protein LC3 as a novel stimulus for macrophage activation. These findings provide new insights into the mechanisms of CVB3-induced macrophage activation and its implications for viral pathogenesis. Full article

(This article belongs to the Special Issue Coxsackieviruses, Polioviruses and Associated Diseases (Second Edition))

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Review

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42 pages, 2059 KiB

Open AccessReview

Myocarditis and Inflammatory Cardiomyopathy in Dilated Heart Failure

by Francesco Nappi

Viruses 2025, 17(4), 484; https://doi.org/10.3390/v17040484 - 27 Mar 2025

Viewed by 754

Abstract

Inflammatory cardiomyopathy is a condition that is characterised by the presence of inflammatory cells in the myocardium, which can lead to a significant deterioration in cardiac function. The etiology of this condition involves multiple factors, both infectious and non-infectious causes. While it is primarily associated with viral infections, other potential causes include bacterial, protozoal, or fungal infections, as well as a wide variety of toxic substances and drugs, and systemic immune-mediated pathological conditions. In spite of comprehensive investigation, the presence of inflammatory cardiomyopathy accompanied by left ventricular dysfunction, heart failure or arrhythmia is indicative of an unfavourable outcome. The reasons for the occurrence of either favourable outcomes, characterised by the absence of residual myocardial injury, or unfavourable outcomes, marked by the development of dilated cardiomyopathy, in patients afflicted by the condition remain to be elucidated. The relative contributions of pathogenic agents, genomic profiles of the host, and environmental factors in disease progression and resolution remain subjects of ongoing discourse. This includes the determination of which viruses function as active inducers and which merely play a bystander role. It remains unknown which changes in the host immune profile are critical in determining the outcome of myocarditis caused by various viruses, including coxsackievirus B3 (CVB3), adenoviruses, parvoviruses B19 and SARS-CoV-2. The objective of this review is unambiguous: to provide a concise summary and comprehensive assessment of the extant evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy. Its focus is exclusively on virus-induced and virus-associated myocarditis. In addition, the extant lacunae of knowledge in this field are identified and the extant experimental models are evaluated, with the aim of proposing future directions for the research domain. This includes differential gene expression that regulates iron and lipid and metabolic remodelling. Furthermore, the current state of knowledge regarding the cardiovascular implications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is also discussed, along with the open questions that remain to be addressed. Full article

(This article belongs to the Special Issue Coxsackieviruses, Polioviruses and Associated Diseases (Second Edition))

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