Major 5'terminally deleted enterovirus populations modulate type I IFN response in acute myocarditis patients and in human cultured cardiomyocytes.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
20 07 2020
20 07 2020
Historique:
received:
27
02
2020
accepted:
15
05
2020
entrez:
21
7
2020
pubmed:
21
7
2020
medline:
22
12
2020
Statut:
epublish
Résumé
Major 5'terminally deleted (5'TD) group-B enterovirus (EV-B) populations were identified in heart biopsies of patients with fulminant myocarditis or dilated cardiomyopathy suggesting that these 5'TD forms are key drivers of host-cell interaction in EV cardiac infections. To date, early emergence of EV-B 5'TD forms and its impact on type 1 IFN response during acute myocarditis remains unknown. Using quantitative RACE-PCR assay, we identified major EV-B 5'TD RNA populations in plasma or heart samples of acute myocarditis cases. Deletions identified within the 5' non-coding region of EV-B populations only affected secondary-structural elements of genomic RNA domain I and were distinguished in two major groups based on the extent of RNA structural deletions. Proportions of these two respective EV-B 5'TD population groups were positively or negatively correlated with IFN-β levels in plasma samples of myocarditis patients. Transfection of synthetic CVB3/28 RNAs harboring various 5'terminal full-length or deleted sequences into human cultured cardiomyocytes demonstrated that viral genomic RNA domain I possessed essential immunomodulatory secondary-structural elements responsible for IFN-β pathway induction. Overall, our results highlight the early emergence of major EVB-TD populations which deletions affecting secondary-structures of RNA domain I can modulate innate immune sensing mechanisms in cardiomyocytes of patients with acute myocarditis.
Identifiants
pubmed: 32686697
doi: 10.1038/s41598-020-67648-5
pii: 10.1038/s41598-020-67648-5
pmc: PMC7371739
doi:
Substances chimiques
5' Untranslated Regions
0
Interferon Type I
0
RNA, Viral
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11947Investigateurs
A Mirand
(A)
C Henquell
(C)
Marie-Laure Mathieu
(ML)
Ellia Mezgueldi
(E)
Matthieu Verdan
(M)
Pascal Motreff
(P)
B Lina
(B)
I Schuffenecker
(I)
Samira Fafi-Kremer
(S)
Quentin Lepiller
(Q)
Patrick Bruneval
(P)
Références
Dennert, R., Crijns, H. J. & Heymans, S. Acute viral myocarditis. Eur. Heart J.29, 2073–2082 (2008).
doi: 10.1093/eurheartj/ehn296
Pallansch, M. A. & Roos, R. Enteroviruses : Polioviruses, Coxsackieviruses, Echoviruses, and Newer Enteroviruses. In Fields Virology Vol. 1 840–893 (Lippincott William & Wilkens Company, 2007).
Racaniello, V. R. Picornaviridae: the viruses and their replication. In Fields Virology Vol. 1 795–838 (Knipe & Howley, 2007).
Chapman, N. M., Kim, K.-S., Drescher, K. M., Oka, K. & Tracy, S. 5’ terminal deletions in the genome of a coxsackievirus B2 strain occurred naturally in human heart. Virology375, 480–491 (2008).
doi: 10.1016/j.virol.2008.02.030
Kim, K.-S. et al. 5’-Terminal deletions occur in coxsackievirus B3 during replication in murine hearts and cardiac myocyte cultures and correlate with encapsidation of negative-strand viral RNA. J. Virol.79, 7024–7041 (2005).
doi: 10.1128/JVI.79.11.7024-7041.2005
Kim, K.-S., Chapman, N. M. & Tracy, S. Replication of coxsackievirus B3 in primary cell cultures generates novel viral genome deletions. J. Virol.82, 2033–2037 (2008).
doi: 10.1128/JVI.01774-07
Bouin, A. et al. Major persistent 5′ terminally deleted coxsackievirus B3 populations in human endomyocardial tissues. Emerg. Infect. Dis.22, 1488–1490 (2016).
doi: 10.3201/eid2208.160186
Bouin, A. et al. Enterovirus persistence in cardiac cells of patients with idiopathic dilated cardiomyopathy is linked to 5’ terminal genomic RNA-deleted viral populations with viral-encoded proteinase activities. Circulation139, 2326–2338 (2019).
doi: 10.1161/CIRCULATIONAHA.118.035966
Feng, Q. et al. MDA5 detects the double-stranded RNA replicative form in picornavirus-infected cells. Cell Rep.2, 1187–1196 (2012).
doi: 10.1016/j.celrep.2012.10.005
Feng, Q. et al. Coxsackievirus cloverleaf RNA containing a 5′ triphosphate triggers an antiviral response via RIG-I activation. PLoS ONE9, e95927 (2014).
doi: 10.1371/journal.pone.0095927
Lévêque, N. et al. Functional Consequences of RNA 5′-Terminal Deletions on Coxsackievirus B3 RNA Replication and Ribonucleoprotein Complex Formation. J. Virol.91, (2017).
Ertel, K. J., Brunner, J. E. & Semler, B. L. Mechanistic consequences of hnRNP C binding to both RNA termini of poliovirus negative-strand RNA intermediates. J. Virol.84, 4229–4242 (2010).
doi: 10.1128/JVI.02198-09
Brunner, J. E., Ertel, K. J., Rozovics, J. M. & Semler, B. L. Delayed kinetics of poliovirus RNA synthesis in a human cell line with reduced levels of hnRNP C proteins. Virology400, 240–247 (2010).
doi: 10.1016/j.virol.2010.01.031
Jaramillo, L., Smithee, S., Tracy, S. & Chapman, N. M. Domain I of the 5′ non-translated genomic region in coxsackievirus B3 RNA is not required for productive replication. Virology496, 127–130 (2016).
doi: 10.1016/j.virol.2016.05.021
Reikine, S., Nguyen, J. B. & Modis, Y. Pattern recognition and signaling mechanisms of RIG-I and MDA5. Fronti Immunol.5, (2014).
Fung, G., Luo, H., Qiu, Y., Yang, D. & McManus, B. Myocarditis. Circ. Res.118, 496–514 (2016).
doi: 10.1161/CIRCRESAHA.115.306573
Lévêque, N. et al. Functional consequences of RNA 5′-terminal deletions on coxsackievirus B3 RNA replication and ribonucleoprotein complex formation. J. Virol.91, e00423-e517 (2017).
doi: 10.1128/JVI.00423-17
Gamarnik, A. V. & Andino, R. Two functional complexes formed by KH domain containing proteins with the 5’ noncoding region of poliovirus RNA. RNA3, 882–892 (1997).
pubmed: 9257647
pmcid: 1369533
Holmblat, B. et al. Nonhomologous recombination between defective poliovirus and coxsackievirus genomes suggests a new model of genetic plasticity for picornaviruses. mBio5, e01119-14 (2014).
doi: 10.1128/mBio.01119-14
Muslin, C., Joffret, M.-L., Pelletier, I., Blondel, B. & Delpeyroux, F. Evolution and emergence of enteroviruses through intra- and inter-species recombination: plasticity and phenotypic impact of modular genetic exchanges in the 5’ untranslated region. PLoS Pathog.11, e1005266 (2015).
doi: 10.1371/journal.ppat.1005266
Vignuzzi, M. & López, C. B. Defective viral genomes are key drivers of the virus–host interaction. Nat. Microbiol.4, 1075–1087 (2019).
doi: 10.1038/s41564-019-0465-y
Sanchez David, R. Y. et al. Comparative analysis of viral RNA signatures on different RIG-I-like receptors. Elife5, e11275 (2016).
doi: 10.7554/eLife.11275
Caforio, A. L. P. et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur. Heart J.34(2636–2648), 2648a–2648d (2013).
Kumar, S., Stecher, G., Li, M., Knyaz, C. & Tamura, K. MEGA X: molecular evolutionary genetics analysis across computing platforms. Mol. Biol. Evol.35, 1547–1549 (2018).
doi: 10.1093/molbev/msy096
Nix, W. A., Oberste, M. S. & Pallansch, M. A. Sensitive, seminested PCR amplification of VP1 sequences for direct identification of all enterovirus serotypes from original clinical specimens. J. Clin. Microbiol.44, 2698–2704 (2006).
doi: 10.1128/JCM.00542-06
Panaro, N. J. et al. Evaluation of DNA fragment sizing and quantification by the agilent 2100 bioanalyzer. Clin. Chem.46, 1851–1853 (2000).
doi: 10.1093/clinchem/46.11.1851
Nachamkin, I. et al. Agilent 2100 bioanalyzer for restriction fragment length polymorphism analysis of the Campylobacter jejuni flagellin gene. J. Clin. Microbiol.39, 754–757 (2001).
doi: 10.1128/JCM.39.2.754-757.2001
Lu, C.-Y., Tso, D.-J., Yang, T., Jong, Y.-J. & Wei, Y.-H. Detection of DNA mutations associated with mitochondrial diseases by Agilent 2100 bioanalyzer. Clin. Chim. Acta 318, 97–105 (2002).
doi: 10.1016/S0009-8981(01)00809-9