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Identification of Interleukin1β as an Amplifier of Interferon alpha-induced Antiviral Responses.

ABSTRACT: The induction of an interferon-mediated response is the first line of defense against pathogens such as viruses. Yet, the dynamics and extent of interferon alpha (IFNα)-induced antiviral genes vary remarkably and comprise three expression clusters: early, intermediate and late. By mathematical modeling based on time-resolved quantitative data, we identified mRNA stability as well as a negative regulatory loop as key mechanisms endogenously controlling the expression dynamics of IFNα-induced antiviral genes in hepatocytes. Guided by the mathematical model, we uncovered that this regulatory loop is mediated by the transcription factor IRF2 and showed that knock-down of IRF2 results in enhanced expression of early, intermediate and late IFNα-induced antiviral genes. Co-stimulation experiments with different pro-inflammatory cytokines revealed that this amplified expression dynamics of the early, intermediate and late IFNα-induced antiviral genes can also be achieved by co-application of IFNα and interleukin1 beta (IL1β). Consistently, we found that IL1β enhances IFNα-mediated repression of viral replication. Conversely, we observed that in IL1β receptor knock-out mice replication of viruses sensitive to IFNα is increased. Thus, IL1β is capable to potentiate IFNα-induced antiviral responses and could be exploited to improve antiviral therapies.

SUBMITTER: Robichon K

PROVIDER: S-EPMC7553310 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Identification of Interleukin1β as an Amplifier of Interferon alpha-induced Antiviral Responses.

Robichon Katharina K Maiwald Tim T Schilling Marcel M Schneider Annette A Willemsen Joschka J Salopiata Florian F Teusel Melissa M Kreutz Clemens C Ehlting Christian C Huang Jun J Chakraborty Sajib S Huang Xiaoyun X Damm Georg G Seehofer Daniel D Lang Philipp A PA Bode Johannes G JG Binder Marco M Bartenschlager Ralf R Timmer Jens J Klingmüller Ursula U

PLoS pathogens 20201001 10

The induction of an interferon-mediated response is the first line of defense against pathogens such as viruses. Yet, the dynamics and extent of interferon alpha (IFNα)-induced antiviral genes vary remarkably and comprise three expression clusters: early, intermediate and late. By mathematical modeling based on time-resolved quantitative data, we identified mRNA stability as well as a negative regulatory loop as key mechanisms endogenously controlling the expression dynamics of IFNα-induced anti ...[more]

PMID: 33002089

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Dataset Information

Identification of Interleukin1β as an Amplifier of Interferon alpha-induced Antiviral Responses.

Publications

Identification of Interleukin1β as an Amplifier of Interferon alpha-induced Antiviral Responses.

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