Early inhibition of hepatocyte innate responses by hepatitis B virus - Centre de recherche en cancérologie de Lyon (UMR INSERM 1052 ; CNRS 5286 ; Centre Léon Bérard) Accéder directement au contenu
Article Dans Une Revue Journal of Hepatology Année : 2015

Early inhibition of hepatocyte innate responses by hepatitis B virus

Barbara Testoni

Résumé

Background & Aims: The outcome of hepatitis B virus (HBV) infection may be influenced by early interactions between the virus and hepatocyte innate immune responses. To date, the study of such interactions during the very early step of infection has not been adequately investigated. Methods: We used the HepaRG cell line, as well as primary human hepatocytes to analyze, within 24 h of exposure to HBV, either delivered by a physiologic route or baculovirus vector (Bac-HBV), the early modulation of the expression of selected antiviral/pro-inflammatory cytokines and interferon stimulated genes. Experiments were also performed in the presence or absence of innate receptor agonists to investigate early HBV-induced blockade of innate responses. Results: We show that hepatocytes themselves could detect HBV, and express innate genes when exposed to either HBV virions or Bac-HBV. Whereas Bac-HBV triggered a strong antiviral cytokine secretion followed by the clearance of replicative intermediates, a physiologic HBV exposure led to an abortive response. The early inhibition of innate response by HBV was mainly evidenced on Toll-like receptor 3 and RIG-I/MDA5 signaling pathways upon engagement with exogenous agonist, leading to a decreased expression of several pro-inflammatory and antiviral cytokine genes. Finally, we demonstrate that this early inhibition of dsRNA-mediated response is due to factor(s) present in the HBV inoculum, but not being HBsAg or HBeAg themselves, and does not require de novo viral protein synthesis and replication. Conclusions: Our data provide strong evidence that HBV viral particles themselves can readily inhibit host innate immune responses upon virion/cell interactions, and may explain, at least partially, the “stealthy” character of HBV.
Fichier principal
Vignette du fichier
1-s2.0-S0168827815004778-main.pdf (818.06 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03315640 , version 1 (12-08-2021)

Identifiants

Citer

Souphalone Luangsay, Marion Gruffaz, Nathalie Isorce, Barbara Testoni, Maud Michelet, et al.. Early inhibition of hepatocyte innate responses by hepatitis B virus. Journal of Hepatology, 2015, 63 (6), pp.1314-1322. ⟨10.1016/j.jhep.2015.07.014⟩. ⟨hal-03315640⟩
149 Consultations
187 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More