Early Emergence of 5′ Terminally Deleted Coxsackievirus-B3 RNA Forms Is Associated with Acute and Persistent Infections in Mouse Target Tissues
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 functio...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/10/8/1203 |
| _version_ | 1797431630666661888 |
|---|---|
| author | Domitille Callon Anne-Laure Lebreil Nicole Bouland Caroline Fichel Paul Fornès Laurent Andreoletti Fatma Berri |
| author_facet | Domitille Callon Anne-Laure Lebreil Nicole Bouland Caroline Fichel Paul Fornès Laurent Andreoletti Fatma Berri |
| author_sort | Domitille Callon |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T09:47:57Z |
| format | Article |
| id | doaj.art-8e30866524aa451eacd1d2230cbeb893 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T09:47:57Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-8e30866524aa451eacd1d2230cbeb8932023-12-02T00:24:58ZengMDPI AGVaccines2076-393X2022-07-01108120310.3390/vaccines10081203Early Emergence of 5′ Terminally Deleted Coxsackievirus-B3 RNA Forms Is Associated with Acute and Persistent Infections in Mouse Target TissuesDomitille Callon0Anne-Laure Lebreil1Nicole Bouland2Caroline Fichel3Paul Fornès4Laurent Andreoletti5Fatma Berri6Cardiovir EA-4684, UFR Médecine, Université de Reims Champagne-Ardenne, 51100 Reims, FranceCardiovir EA-4684, UFR Médecine, Université de Reims Champagne-Ardenne, 51100 Reims, FranceLaboratoire d’Anatomie Pathologique, UFR Médecine, Université de Reims Champagne-Ardenne, 51100 Reims, FranceLaboratoire d’Anatomie Pathologique, UFR Médecine, Université de Reims Champagne-Ardenne, 51100 Reims, FranceCardiovir EA-4684, UFR Médecine, Université de Reims Champagne-Ardenne, 51100 Reims, FranceCardiovir EA-4684, UFR Médecine, Université de Reims Champagne-Ardenne, 51100 Reims, FranceCardiovir EA-4684, UFR Médecine, Université de Reims Champagne-Ardenne, 51100 Reims, FranceMajor 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.https://www.mdpi.com/2076-393X/10/8/1203enteroviruspersistentDBA/2J mouse5′ terminal genomic deletion |
| spellingShingle | Domitille Callon Anne-Laure Lebreil Nicole Bouland Caroline Fichel Paul Fornès Laurent Andreoletti Fatma Berri Early Emergence of 5′ Terminally Deleted Coxsackievirus-B3 RNA Forms Is Associated with Acute and Persistent Infections in Mouse Target Tissues Vaccines enterovirus persistent DBA/2J mouse 5′ terminal genomic deletion |
| title | Early Emergence of 5′ Terminally Deleted Coxsackievirus-B3 RNA Forms Is Associated with Acute and Persistent Infections in Mouse Target Tissues |
| title_full | Early Emergence of 5′ Terminally Deleted Coxsackievirus-B3 RNA Forms Is Associated with Acute and Persistent Infections in Mouse Target Tissues |
| title_fullStr | Early Emergence of 5′ Terminally Deleted Coxsackievirus-B3 RNA Forms Is Associated with Acute and Persistent Infections in Mouse Target Tissues |
| title_full_unstemmed | Early Emergence of 5′ Terminally Deleted Coxsackievirus-B3 RNA Forms Is Associated with Acute and Persistent Infections in Mouse Target Tissues |
| title_short | Early Emergence of 5′ Terminally Deleted Coxsackievirus-B3 RNA Forms Is Associated with Acute and Persistent Infections in Mouse Target Tissues |
| title_sort | early emergence of 5 terminally deleted coxsackievirus b3 rna forms is associated with acute and persistent infections in mouse target tissues |
| topic | enterovirus persistent DBA/2J mouse 5′ terminal genomic deletion |
| url | https://www.mdpi.com/2076-393X/10/8/1203 |
| work_keys_str_mv | AT domitillecallon earlyemergenceof5terminallydeletedcoxsackievirusb3rnaformsisassociatedwithacuteandpersistentinfectionsinmousetargettissues AT annelaurelebreil earlyemergenceof5terminallydeletedcoxsackievirusb3rnaformsisassociatedwithacuteandpersistentinfectionsinmousetargettissues AT nicolebouland earlyemergenceof5terminallydeletedcoxsackievirusb3rnaformsisassociatedwithacuteandpersistentinfectionsinmousetargettissues AT carolinefichel earlyemergenceof5terminallydeletedcoxsackievirusb3rnaformsisassociatedwithacuteandpersistentinfectionsinmousetargettissues AT paulfornes earlyemergenceof5terminallydeletedcoxsackievirusb3rnaformsisassociatedwithacuteandpersistentinfectionsinmousetargettissues AT laurentandreoletti earlyemergenceof5terminallydeletedcoxsackievirusb3rnaformsisassociatedwithacuteandpersistentinfectionsinmousetargettissues AT fatmaberri earlyemergenceof5terminallydeletedcoxsackievirusb3rnaformsisassociatedwithacuteandpersistentinfectionsinmousetargettissues |