Infections persistantes à entérovirus et pathologies humaines

Enteroviruses (EVs) are small naked single-stranded positive RNA viruses (Picornaviridae) of approximately 7,400 nucleotides divided in four species (HEV A-D) and including 120 serotypes. EVs are common human pathogens, transmitted through fecal-oral and respiratory routes. Although the majority of EV infections remains asymptomatic (90 %), these viruses are considered as one of the most common causes of acute viral illnesses in immunocompetent pediatric and adult subjects. High levels of genetic diversity allow these viruses to infect various target cells resulting in a wide spectrum of human acute pathologies including meningitis, respiratory syndromes, cutaneous syndromes, myocarditis and mother-to-child infections. During the early phases of the acute viral infection, EV can modulate the non-specific antiviral strategies developed by the infected target cell (modulation of class I MHC viral antigen presentation ; inhibition of type I interferon expression genes) and to disturb dendritic cell functions resulting in a viral immune escape. This immunological escape allows the generation of genetically modified viruses resulting from RNA genomic deletions, mutations or recombination mechanisms. Persistent replication activities of these genetically modified viruses can induce modulation of specific functions and endocellular pathways of infected cells and the development of chronic inflammatory or autoimmune mechanisms (auto-reactive T and -B cells and auto-antibodies). The persistence of these genetically modified viruses can result in direct or indirect tissue injuries that can explain a subset of chronic myocarditis and dilated cardiomyopathy (DCM), type 1 diabetes mellitus and post-polio syndrome (PPS) cases. Actually no specific and curative therapies are available against EV-induced chronic human pathologies. A better understanding of the molecular mechanisms implicated in viral persistence will stimulate the research into new therapeutic strategies to prevent and treat chronic infections caused by EVs.