Interferon-beta expression and type I interferon receptor signaling of hepatocytes prevent hepatic necrosis and virus dissemination in Coxsackievirus B3-infected mice.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Detje, Claudia N
Langereis, Martijn A
Vondran, Florian W R
van Kuppeveld, Frank J M
MetadataShow full item record
AbstractDuring Coxsackievirus B3 (CVB3) infection hepatitis is a potentially life threatening complication, particularly in newborns. Studies with type I interferon (IFN-I) receptor (IFNAR)-deficient mice revealed a key role of the IFN-I axis in the protection against CVB3 infection, whereas the source of IFN-I and cell types that have to be IFNAR triggered in order to promote survival are still unknown. We found that CVB3 infected IFN-β reporter mice showed effective reporter induction, especially in hepatocytes and only to a minor extent in liver-resident macrophages. Accordingly, upon in vitro CVB3 infection of primary hepatocytes from murine or human origin abundant IFN-β responses were induced. To identify sites of IFNAR-triggering we performed experiments with Mx reporter mice, which upon CVB3 infection showed massive luciferase induction in the liver. Immunohistological studies revealed that during CVB3 infection MX1 expression of hepatocytes was induced primarily by IFNAR-, and not by IFN-III receptor (IFNLR)-triggering. CVB3 infection studies with primary human hepatocytes, in which either the IFN-I or the IFN-III axis was inhibited, also indicated that primarily IFNAR-, and to a lesser extent IFNLR-triggering was needed for ISG induction. Interestingly, CVB3 infected mice with a hepatocyte-specific IFNAR ablation showed severe liver cell necrosis and ubiquitous viral dissemination that resulted in lethal disease, as similarly detected in classical IFNAR-/- mice. In conclusion, we found that during CVB3 infection hepatocytes are major IFN-I producers and that the liver is also the organ that shows strong IFNAR-triggering. Importantly, hepatocytes need to be IFNAR-triggered in order to prevent virus dissemination and to assure survival. These data are compatible with the hypothesis that during CVB3 infection hepatocytes serve as important IFN-I producers and sensors not only in the murine, but also in the human system.
AffiliationTWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 3.0 United States
- Type I interferon receptor signaling delays Kupffer cell replenishment during acute fulminant viral hepatitis.
- Authors: Borst K, Frenz T, Spanier J, Tegtmeyer PK, Chhatbar C, Skerra J, Ghita L, Namineni S, Lienenklaus S, Köster M, Heikenwaelder M, Sutter G, Kalinke U
- Issue date: 2018 Apr
- Alpha/Beta Interferon (IFN-α/β) Signaling in Astrocytes Mediates Protection against Viral Encephalomyelitis and Regulates IFN-γ-Dependent Responses.
- Authors: Hwang M, Bergmann CC
- Issue date: 2018 May 15
- MicroRNA-30a Modulates Type I Interferon Responses to Facilitate Coxsackievirus B3 Replication <i>Via</i> Targeting Tripartite Motif Protein 25.
- Authors: Li J, Xie Y, Li L, Li X, Shen L, Gong J, Zhang R
- Issue date: 2020
- MAVS-dependent IRF3/7 bypass of interferon β-induction restricts the response to measles infection in CD150Tg mouse bone marrow-derived dendritic cells.
- Authors: Takaki H, Honda K, Atarashi K, Kobayashi F, Ebihara T, Oshiumi H, Matsumoto M, Shingai M, Seya T
- Issue date: 2014 Feb
- In Vivo Conditions Enable IFNAR-Independent Type I Interferon Production by Peritoneal CD11b+ Cells upon Thogoto Virus Infection.
- Authors: Kochs G, Anzaghe M, Kronhart S, Wagner V, Gogesch P, Scheu S, Lienenklaus S, Waibler Z
- Issue date: 2016 Oct 15