Special Issue "Enteroviruses 2021"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (15 October 2021).

Special Issue Editor

Prof. Dr. Hung-Yao Ho
E-Mail Website
Guest Editor
Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taiwan
Interests: host-enterovirus interactions, with emphasis on the roles of mitochondria and metabolic reprogramming in viral pathogenesis

Special Issue Information

Dear Colleagues,

Many enteroviruses are important pathogens that can cause human diseases. Within the genus Enterovirus, there are 15 species including Enterovirus A-L and Rhinovirus A-C.

Of human pathogens, Enterovirus A71 (EV-A71) is an important causative agent of hand, foot and mouth disease (HFMD), and can cause serious neural complications. It has caused epidemics in various parts of the world in recent decades. Though a vaccine is currently available, more about the host–enterovirus interaction and the host innate immune response to enterovirus, and the underlying molecular mechanism can be learned from the study of EV-A71. Enterovirus D68 (EV-D68) caused an outbreak in the United States in 2004, and spread to other countries. EV-D68 infection is associated with respiratory symptoms, and potentially leads to acute flaccid myelitis in children. Other viruses cause diseases, such as myocarditis, pericarditis, conjunctivitis, etc.

Given the clinical significance of enteroviruses, this Special Issue will explore the molecular aspects of viral pathogenesis, the host responses to enteroviruses, the application of omics technologies to the study of enteroviruses, and the development of vaccines and antivirals against enteroviruses. 

Prof. Dr. Hung-Yao Ho
Guest Editor

Manuscript Submission Information

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Keywords

  • Enterovirus
  • Rhinovirus
  • Pathogenesis
  • Omics technologies
  • Host–virus interaction
  • Innate immunity
  • Vaccine
  • Antiviral

Published Papers (6 papers)

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Research

Article
Wastewater-Based Epidemiology and Long-Read Sequencing to Identify Enterovirus Circulation in Three Municipalities in Maricopa County, Arizona, Southwest United States between June and October 2020
Viruses 2021, 13(9), 1803; https://0-doi-org.brum.beds.ac.uk/10.3390/v13091803 - 10 Sep 2021
Viewed by 542
Abstract
We used wastewater-based epidemiology and amplicon-based long-read high-throughput sequencing for surveillance of enteroviruses (EVs) in Maricopa County, Arizona, Southwest United States. We collected 48 samples from 13 sites in three municipalities between 18 June and 1 October 2020, and filtered (175 mL each; [...] Read more.
We used wastewater-based epidemiology and amplicon-based long-read high-throughput sequencing for surveillance of enteroviruses (EVs) in Maricopa County, Arizona, Southwest United States. We collected 48 samples from 13 sites in three municipalities between 18 June and 1 October 2020, and filtered (175 mL each; 0.45 µm pore size) and extracted RNA from the filter-trapped solids. The RNA was converted to cDNA and processed through two workflows (Sanger sequencing (SSW) and long-read Illumina sequencing (LRISW)) each including a nested polymerase chain reaction (nPCR) assay. We subjected the ~350 bp amplicon from SSW to Sanger sequencing and the ~1900–2400 bp amplicon from LRISW to Illumina sequencing. We identified EV contigs from 11 of the 13 sites and 41.67% (20/48) of screened samples. Using the LRISW, we detected nine EV genotypes from three species (Enterovirus A (CVA4, EV-A76, EV-A90), Enterovirus B (E14) and Enterovirus C (CVA1, CVA11, CVA13, CVA19 and CVA24)) with Enterovirus C representing approximately 90% of the variants. However, the SSW only detected the five Enterovirus C types. Similarity and phylogenetic analysis showed that multiple Enterovirus C lineages were circulating, co-infecting and recombining in the population during the season despite the SARS-CoV-2 pandemic and the non-pharmaceutical public health measures taken to curb transmission. Full article
(This article belongs to the Special Issue Enteroviruses 2021)
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Article
High Heterogeneity of Echoviruses in Brazilian Children with Acute Gastroenteritis
Viruses 2021, 13(4), 595; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040595 - 31 Mar 2021
Viewed by 719
Abstract
Echoviruses (E) are a diverse group of viruses responsible for various pathological conditions in humans including aseptic meningitis, myocarditis, and acute flaccid paralysis. The detection and identification of echovirus genotypes in clinical samples is challenging due to its high genetic diversity. Here, we [...] Read more.
Echoviruses (E) are a diverse group of viruses responsible for various pathological conditions in humans including aseptic meningitis, myocarditis, and acute flaccid paralysis. The detection and identification of echovirus genotypes in clinical samples is challenging due to its high genetic diversity. Here, we report the complete genome sequences of nine echoviruses, obtained by next-generation sequencing of 238 fecal samples from individuals with gastroenteritis in regions of Brazil. Detected viruses were classified into six genotypes: Three E1 sequences (BRA/TO-028, BRA/TO-069 and BRA/TO-236), one E3 (BRA/TO-018), one E11 (BRA/TO-086), one E20 (BRA/TO-016), two E29 (BRA/TO-030 and BRA/TO-193), and one E30 sequence (BRA/TO-032). Phylogenetic analysis indicated that the echoviruses E1 and E29 circulating in Brazil are divergent from strains circulating worldwide. The genotype diversity identified in our study may under-represent the total echovirus diversity in Brazil because of the small sample size and the restricted geographical distribution covered by the survey. Full article
(This article belongs to the Special Issue Enteroviruses 2021)
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Article
Inhibition of Enterovirus A71 by a Novel 2-Phenyl-Benzimidazole Derivative
Viruses 2021, 13(1), 58; https://0-doi-org.brum.beds.ac.uk/10.3390/v13010058 - 04 Jan 2021
Cited by 1 | Viewed by 628
Abstract
Enterovirus A71 (EV-A71) infection has emerged as a significant public health concern at the global level. Epidemic events of EV-A71 have been reported worldwide, and this succession of outbreaks has heightened concern that EV-A71 may become a public health threat. In recent years, [...] Read more.
Enterovirus A71 (EV-A71) infection has emerged as a significant public health concern at the global level. Epidemic events of EV-A71 have been reported worldwide, and this succession of outbreaks has heightened concern that EV-A71 may become a public health threat. In recent years, widespread A71 enterovirus also occurred in European countries. EV-A71 infection causes hand-foot-mouth disease (HFMD), herpangina, and fever. However, it can sometimes induce a variety of neurological complications, including encephalitis, aseptic meningitis, pulmonary edema, and acute flaccid paralysis. We identified new benzimidazole derivatives and described theirin vitrocytotoxicity and broad-spectrum anti-enterovirus activity. Among them, derivative 2b resulted in interesting activity against EV-A71, and therefore it was selected for further investigations. Compound 2b proved to be able to protect cell monolayers from EV-A71-induced cytopathogenicity, with an EC50 of 3 µM. Moreover, Vero-76 cells resulted in being significantly protected from necrosis and apoptosis when treated with 2b at 20 and 80 µM. Compound 2b reduced viral adsorption to Vero-76 cells, and when evaluated in a time-of-addition assay, the derivative had the highest effect when added during the infection period. Moreover, derivative 2b reduced viral penetration into host cells. Besides, 2b did not affect intestinal monolayers permeability, showing no toxic effects. A detailed insight into the efficacy of compound 2b against EV-A71 showed a dose-dependent reduction in the viral titer, also at low concentrations. Mechanism of action investigations suggested that our derivative can inhibit viral endocytosis by reducing viral attachment to and penetration into host cells. Pharmacokinetic and toxicity predictions validated compound 2b as a good candidate for furtherin vivoassays. Full article
(This article belongs to the Special Issue Enteroviruses 2021)
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Article
New RNA Structural Elements Identified in the Coding Region of the Coxsackie B3 Virus Genome
Viruses 2020, 12(11), 1232; https://0-doi-org.brum.beds.ac.uk/10.3390/v12111232 - 30 Oct 2020
Viewed by 595
Abstract
Here we present a set of new structural elements formed within the open reading frame of the virus, which are highly probable, evolutionarily conserved and may interact with host proteins. This work focused on the coding regions of the CVB3 genome (particularly the [...] Read more.
Here we present a set of new structural elements formed within the open reading frame of the virus, which are highly probable, evolutionarily conserved and may interact with host proteins. This work focused on the coding regions of the CVB3 genome (particularly the V4-, V1-, 2C-, and 3D-coding regions), which, with the exception of the cis-acting replication element (CRE), have not yet been subjected to experimental analysis of their structures. The SHAPE technique, chemical modification with DMS and RNA cleavage with Pb2+, were performed in order to characterize the RNA structure. The experimental results were used to improve the computer prediction of the structural models, whereas a phylogenetic analysis was performed to check universality of the newly identified structural elements for twenty CVB3 genomes and 11 other enteroviruses. Some of the RNA motifs turned out to be conserved among different enteroviruses. We also observed that the 3′-terminal region of the genome tends to dimerize in a magnesium concentration-dependent manner. RNA affinity chromatography was used to confirm RNA–protein interactions hypothesized by database searches, leading to the discovery of several interactions, which may be important for virus propagation. Full article
(This article belongs to the Special Issue Enteroviruses 2021)
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Article
Mapping Attenuation Determinants in Enterovirus-D68
Viruses 2020, 12(8), 867; https://0-doi-org.brum.beds.ac.uk/10.3390/v12080867 - 08 Aug 2020
Viewed by 1701
Abstract
Enterovirus (EV)-D68 has been associated with epidemics in the United Sates in 2014, 2016 and 2018. This study aims to identify potential viral virulence determinants. We found that neonatal type I interferon receptor knockout mice are susceptible to EV-D68 infection via intraperitoneal inoculation [...] Read more.
Enterovirus (EV)-D68 has been associated with epidemics in the United Sates in 2014, 2016 and 2018. This study aims to identify potential viral virulence determinants. We found that neonatal type I interferon receptor knockout mice are susceptible to EV-D68 infection via intraperitoneal inoculation and were able to recapitulate the paralysis process observed in human disease. Among the EV-D68 strains tested, strain US/MO-14-18949 caused no observable disease in this mouse model, whereas the other strains caused paralysis and death. Sequence analysis revealed several conserved genetic changes among these virus strains: nucleotide positions 107 and 648 in the 5′-untranslated region (UTR); amino acid position 88 in VP3; 1, 148, 282 and 283 in VP1; 22 in 2A; 47 in 3A. A series of chimeric and point-mutated infectious clones were constructed to identify viral elements responsible for the distinct virulence. A single amino acid change from isoleucine to valine at position 88 in VP3 attenuated neurovirulence by reducing virus replication in the brain and spinal cord of infected mice. Full article
(This article belongs to the Special Issue Enteroviruses 2021)
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Article
Whole-Genome Sequencing of Human Enteroviruses from Clinical Samples by Nanopore Direct RNA Sequencing
Viruses 2020, 12(8), 841; https://0-doi-org.brum.beds.ac.uk/10.3390/v12080841 - 31 Jul 2020
Cited by 2 | Viewed by 1650
Abstract
Enteroviruses are small RNA viruses that affect millions of people each year by causing an important burden of disease with a broad spectrum of symptoms. In routine diagnostic laboratories, enteroviruses are identified by PCR-based methods, often combined with partial sequencing for genotyping. In [...] Read more.
Enteroviruses are small RNA viruses that affect millions of people each year by causing an important burden of disease with a broad spectrum of symptoms. In routine diagnostic laboratories, enteroviruses are identified by PCR-based methods, often combined with partial sequencing for genotyping. In this proof-of-principle study, we assessed direct RNA sequencing (DRS) using nanopore sequencing technology for fast whole-genome sequencing of viruses directly from clinical samples. The approach was complemented by sequencing the corresponding viral cDNA via Illumina MiSeq sequencing. DRS of total RNA extracted from three different enterovirus-positive stool samples produced long RNA fragments, covering between 59% and 99.6% of the most similar reference genome sequences. The identification of the enterovirus sequences in the samples was confirmed by short-read cDNA sequencing. Sequence identity between DRS and Illumina MiSeq enterovirus consensus sequences ranged between 94% and 97%. Here, we show that nanopore DRS can be used to correctly identify enterovirus genotypes from patient stool samples with high viral load and that the approach also provides rich metatranscriptomic information on sample composition for all life domains. Full article
(This article belongs to the Special Issue Enteroviruses 2021)
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