EV-B 3D polymerase remodels viral populations through 5′UTR recombination to subvert cardiac antiviral innate immunity
Abstract
Viral myocarditis, a leading cause of morbidity in young populations, is strongly linked to Coxsackievirus B (CV-B) infections harboring dominant 5′-terminally deleted (5′TD) and minor full-length (FL) CV-B RNA populations in cardiac tissues. Here, we demonstrate how viral RNA-dependent RNA polymerase (3Dpol)-driven recombination in the 5′UTR orchestrates viral RNA populations dynamics and subverts type I interferon responses. In primary human cardiomyocytes (HCMs), 3Dpol-mediated copy-choice recombination enhances 5′TD RNA replication while suppressing FL populations. Infection of immunocompetent mice with recombination-deficient CV-B3 (3Dpol Y276H) shifted 5′TD populations ratios toward immune-sensing viral RNAs, elevating cardiac IFN-β/ISG15 and accelerating viral clearance. Transfection experiments confirmed that 50-nt 5′TD RNAs (TD50) evade innate immunity, whereas shorter deletions (9–36-nt, TD15) restore type I interferon responses in HCMs. Our findings establish 3Dpol-driven recombination as a critical mechanism sustaining pathogenic 5′TD RNAs that subvert antiviral innate immunity, highlighting recombination inhibition as a promising therapeutic strategy against CV-B myocarditis.
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BibTeX
@article{glenet2026polymerase,
title = {{EV-B 3D polymerase remodels viral populations through 5′UTR recombination to subvert cardiac antiviral innate immunity}},
author = {Marie Glenet and Laetitia Heng and Anne-Laure Lebreil and Paul-Antoine Gretteau and Yohan Nguyen and Fatma Berri and Laurent Andreoletti},
journal = {PLoS Pathogens},
year = {2026},
month = jul,
url = {https://univ-reims.hal.science/hal-05799478v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - EV-B 3D polymerase remodels viral populations through 5′UTR recombination to subvert cardiac antiviral innate immunity
AU - Marie Glenet
AU - Laetitia Heng
AU - Anne-Laure Lebreil
AU - Paul-Antoine Gretteau
AU - Yohan Nguyen
AU - Fatma Berri
AU - Laurent Andreoletti
PY - 2026
DA - 2026/07/24
JO - PLoS Pathogens
UR - https://univ-reims.hal.science/hal-05799478v1
AB - Viral myocarditis, a leading cause of morbidity in young populations, is strongly linked to Coxsackievirus B (CV-B) infections harboring dominant 5′-terminally deleted (5′TD) and minor full-length (FL) CV-B RNA populations in cardiac tissues. Here, we demonstrate how viral RNA-dependent RNA polymerase (3Dpol)-driven recombination in the 5′UTR orchestrates viral RNA populations dynamics and subverts type I interferon responses. In primary human cardiomyocytes (HCMs), 3Dpol-mediated copy-choice recombination enhances 5′TD RNA replication while suppressing FL populations. Infection of immunocompetent mice with recombination-deficient CV-B3 (3Dpol Y276H) shifted 5′TD populations ratios toward immune-sensing viral RNAs, elevating cardiac IFN-β/ISG15 and accelerating viral clearance. Transfection experiments confirmed that 50-nt 5′TD RNAs (TD50) evade innate immunity, whereas shorter deletions (9–36-nt, TD15) restore type I interferon responses in HCMs. Our findings establish 3Dpol-driven recombination as a critical mechanism sustaining pathogenic 5′TD RNAs that subvert antiviral innate immunity, highlighting recombination inhibition as a promising therapeutic strategy against CV-B myocarditis.
SN - 1553-7366
SN - 1553-7374
ER -