Activation of Nod2 signalling upon Norovirus infection enhances antiviral immunity and susceptibility to colitis - Centre de recherche en cancérologie de Lyon (UMR INSERM 1052 ; CNRS 5286 ; Centre Léon Bérard) Accéder directement au contenu
Pré-Publication, Document De Travail (Working Paper) Année : 2023

Activation of Nod2 signalling upon Norovirus infection enhances antiviral immunity and susceptibility to colitis

Résumé

Over 90% of epidemic nonbacterial gastroenteritis are caused by human Noroviruses (NoV) which are persisting in a substantial subset of people allowing their spread worldwide. It leads to a significant number of endemic cases and up to 70,000 children deaths in developing countries. NoVs are primarily transmitted through the fecal-oral route. To date studies have focused on the influence of the gut microbiota on viral clearance by enteric immunity. In this study, the use of the persistent mouse Norovirus S99 strain (MNoV_S99) allowed us to provide evidence that the norovirus-driven exacerbation of colitis severity relied on bacterial sensing by nucleotide-binding oligomerization domain 2 (Nod2). Similarly, another persistent MNoV_CR6 strain failed to exacerbate colitis severity in Nod2-deficient mice. In parallel, the viremia was heightened in these mice in comparison with control animals. Accordingly, a reduced level of phosphorylation of Signal Transducer and Activator of Transcription1 (STAT1) in Nod2-deficient macrophages infected by MNoV_S99 was measured. By contrast, STAT1 phosphorylation was increased in wild-type macrophages and associated with an induction of NOD2 expression. This in turn enhances myeloid cells response to muramyl dipeptide (MDP) resulting in downstream pro-inflammatory cytokine secretion and reduced noroviral production. Hence, our results uncover a previously unidentified virus-host-bacterial interplay that may represent a novel therapeutic target for treating noroviral origin gastroenteritis that may be linked with susceptibility to several common illnesses such as Crohn’s disease.
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Dates et versions

hal-04101382 , version 1 (22-05-2023)
hal-04101382 , version 2 (13-08-2023)
hal-04101382 , version 3 (30-10-2023)

Identifiants

  • HAL Id : hal-04101382 , version 1

Citer

Ghaffar Muharram, Marion Thépaut, Pierre-Emmanuel Lobert, Teddy Grandjean, Olivier Boulard, et al.. Activation of Nod2 signalling upon Norovirus infection enhances antiviral immunity and susceptibility to colitis. 2023. ⟨hal-04101382v1⟩
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