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Réémergence virale épidémique : coxsackievirus A6 et entérovirus A71, de la maladie pied-main-bouche aux atteintes neurologiques

Abstract : Enteroviruses (EVs) are enteric viruses assigned to the Picornaviridae family and classified into four taxonomic species (A to D). Symptomatic EV infections can be associated with diseases of the nervous system, lung, heart, muscle, and skin. Hand-foot-and-mouth disease (HFMD) is characterized by a rash and oral ulcerations in children under 5 years. Enterovirus A71 (EVA71) and coxsackievirus A6 (CVA6) are the two most frequent EV types of species A reported in HFMD cases. In France, EVA71 was associated with an increasing number of neurological diseases since 2016, and CVA6 was associated with regular HFMD outbreaks. The main aim of the thesis is to investigate and compare the epidemic reemergences of these two viruses by using whole-genome analysis. The outbreak of neurological diseases in 2016 was associated with the virus C1v2015 assigned to the EVA71 subgenogroup C1, which emerged in 2010. This virus has a chimeric genome characterized by multiple recombination events. Compared with the genomes of the earlier C1 viruses, the C1v2015 genome displays characteristic changes within epitopes exposed at the capsid surface. The recombination event that changed in 2013 the 3Dpol gene occurred shortly before the epidemic spread in Europe in 2015. To investigate CVA6, we designed a whole-genome amplification technique and used high throughput sequencing to determine viral genomes in buccal specimens collected in France between 2010 and 2018. We did not find major variations in structural genes, but we identified five recombinant forms not previously reported by the study of the 3Dpol gene. Paralleling the worldwide shifts, the clinical and epidemiological features of HFMD cases reported in France indicated the epidemic reemergence of CVA6 was contemporaneous of the increasing frequency of an atypical disease. To conclude, our data highlight the value of whole-genome analysis to compare molecular variations and trace the evolutionary and epidemic histories of reemerging enteroviruses.
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Submitted on : Wednesday, July 6, 2022 - 1:02:11 AM
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Stéphanie Tomba Ngangas. Réémergence virale épidémique : coxsackievirus A6 et entérovirus A71, de la maladie pied-main-bouche aux atteintes neurologiques. Médecine humaine et pathologie. Université Clermont Auvergne, 2021. Français. ⟨NNT : 2021UCFAC043⟩. ⟨tel-03714852⟩

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