Molecular Mechanisms of Human Persistent Enterovirus Infections

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (28 May 2022) | Viewed by 6318

Special Issue Editor


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Guest Editor
Department of Infections Cardiovasculaires virales et Inflammation en Pathologie Humaine (CARDIOVIR), Université de Reims Champagne-Ardenne, Reims, France
Interests: enterovirus; positive single-strand RNA; persistence; molecular mechanisms; virus-cell interaction; inflammation; immunity; escape to immune system
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Special Issue Information

Dear Colleagues,

Human enteroviruses (EVs) belong to the Picornaviridae family, a highly diverse group of small, non-enveloped, icosahedral-shaped viruses with single positive-strand RNA genomes. EV species (A to D) are recognized as major causes of human diseases, particularly in neonates and young children where infections can range from acute, self-limited febrile illness to meningitis, myocarditis, hepatitis, and acute flaccid myelitis. As other RNA viruses, EVs have been shown to develop persistent infections of some target tissues resulting in chronic diseases such as myositis, type 1 diabetes, chronic myocarditis and dilated cardiomyopathy. Emergence and maintenance of persistent EV RNA forms during acute infection depend on early host–virus interactions mechanisms and to the virus ability to develop strategies to escape  host immune responses. The combination of low-level replication and translation activities of persistent viruses, associated with the capacity of these RNA forms to early modulate inflammatory mechanisms such as type-I IFN response activation pathway, could explain  how EVs can establish a persistent infection in human target cells. The present review proposes to dissect cellular and viral molecular mechanisms underlying establishment and maintenance of persistent EV infections. Taken together, our contribution to this special issue is expected to stimulate research and development of further preventive or curative strategies to fight against persistent EV infections driving the development of severe human chronic diseases.

Dr. Laurent Andreoletti
Guest Editor

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Keywords

  • enterovirus
  • positive single-strand RNA
  • persistence
  • molecular mechanisms
  • virus-cell interaction
  • inflammation
  • immunity
  • escape to immune system

Published Papers (3 papers)

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Research

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15 pages, 2501 KiB  
Article
Early Emergence of 5′ Terminally Deleted Coxsackievirus-B3 RNA Forms Is Associated with Acute and Persistent Infections in Mouse Target Tissues
by Domitille Callon, Anne-Laure Lebreil, Nicole Bouland, Caroline Fichel, Paul Fornès, Laurent Andreoletti and Fatma Berri
Vaccines 2022, 10(8), 1203; https://doi.org/10.3390/vaccines10081203 - 28 Jul 2022
Cited by 1 | Viewed by 1457
Abstract
Major EV-B populations characterized by 5′ terminal deletions (5′TD) have been shown to be associated with the development of myocarditis and type 1 diabetes in mice or humans. To date, the dynamics of EV-B 5′TD-RNA forms’ emergence during the course of infection and [...] Read more.
Major EV-B populations characterized by 5′ terminal deletions (5′TD) have been shown to be associated with the development of myocarditis and type 1 diabetes in mice or humans. To date, the dynamics of EV-B 5′TD-RNA forms’ emergence during the course of infection and their impact on cellular functions remain unclear. Using a RACE-PCR approach in CVB3/28-infected mouse organs, we showed an early (3 days post infection, DPI) emergence of major 5′TD populations associated with minor full-length RNA forms. Viral replication activities with infectious particle production were associated with heart, liver, and pancreas acute inflammatory lesions, whereas clearance of viral RNA without organ lesions was observed in the brain, lung, intestines, and muscles from 3 to 7 DPI. At 28 DPI, low viral RNA levels, +/-RNA ratios < 5 associated with viral protein 1 expression revealed a persistent infection in the heart and pancreas. This persistent infection was characterized by molecular detection of only 5′TD RNA forms that were associated with dystrophin cleavage in the heart and insulin production impairment in beta-pancreatic cells. These results demonstrated that major EV-B 5′TD RNA forms can be early selected during systemic infection and that their maintenance may drive EV-induced acute and persistent infections with target cell dysfunctions. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Human Persistent Enterovirus Infections)
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9 pages, 1246 KiB  
Article
Molecular Epidemiology of Enterovirus A71 in Surveillance of Acute Flaccid Paralysis Cases in Senegal, 2013–2020
by Ndack Ndiaye, Fatou Diène Thiaw, Amary Fall, Ousmane Kébé, Khadija Leila Diatta, Ndongo Dia, Malick Fall, Amadou Alpha Sall, Martin Faye and Ousmane Faye
Vaccines 2022, 10(6), 843; https://doi.org/10.3390/vaccines10060843 - 25 May 2022
Cited by 3 | Viewed by 1634
Abstract
Enterovirus A71 (EV-A71) is a non-polio enterovirus that currently represents a major public health concern worldwide. In Africa, only sporadic cases have been reported. Acute flaccid paralysis and environmental surveillance programs have been widely used as strategies for documenting the circulation of polio [...] Read more.
Enterovirus A71 (EV-A71) is a non-polio enterovirus that currently represents a major public health concern worldwide. In Africa, only sporadic cases have been reported. Acute flaccid paralysis and environmental surveillance programs have been widely used as strategies for documenting the circulation of polio and non-polio enteroviruses. To date, little is known about the molecular epidemiology of enterovirus A71 in Africa where resources and diagnostic capacities are limited. To fill this gap in Senegal, a total of 521 non-polio enterovirus isolates collected from both acute flaccid paralysis (AFP) and environmental surveillance (ES) programs between 2013 and 2020 were screened for enterovirus A71 using real-time RT-PCR. Positive isolates were sequenced, and genomic data were analyzed using phylogeny. An overall rate of 1.72% (9/521) of the analyzed isolates tested positive for enterovirus A71. All positive isolates originated from the acute flaccid paralysis cases, and 44.4% (4/9) of them were isolated in 2016. The nine newly characterized sequences obtained in our study included eight complete polyprotein sequences and one partial sequence of the VP1 gene, all belonging to the C genogroup. Seven out of the eight complete polyprotein sequences belonged to the C2 subgenotype, while one of them grouped with previous sequences from the C1 subgenotype. The partial VP1 sequence belonged to the C1 subgenotype. Our data provide not only new insights into the recent molecular epidemiology of enterovirus A71 in Senegal but also point to the crucial need to set up specific surveillance programs targeting non-polio enteroviruses at country or regional levels in Africa for rapid identification emerging or re-emerging enteroviruses and better characterization of public health concerns causing acute flaccid paralysis in children such as enterovirus A71. To estimate the real distribution of EV-A71 in Africa, more sero-epidemiological studies should be promoted, particularly in countries where the virus has already been reported. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Human Persistent Enterovirus Infections)
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Review

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28 pages, 2366 KiB  
Review
Persistent Enterovirus Infection: Little Deletions, Long Infections
by Nora M. Chapman
Vaccines 2022, 10(5), 770; https://doi.org/10.3390/vaccines10050770 - 12 May 2022
Cited by 7 | Viewed by 2442
Abstract
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) [...] Read more.
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. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Human Persistent Enterovirus Infections)
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