Induction of GADD34 Is Necessary for dsRNA-Dependent Interferon-β Production and Participates in the Control of Chikungunya Virus Infection

Nucleic acid sensing by cells is a key feature of antiviral responses, which generally result in type-I Interferon production and tissue protection. However, detection of double-stranded RNAs in virus-infected cells promotes two concomitant and apparently conflicting events. The dsRNA-dependent protein kinase (PKR) phosphorylates translation initiation factor 2-alpha (eIF2α) and inhibits protein synthesis, whereas cytosolic DExD/H box RNA helicases induce expression of type I-IFN and other cytokines. We demonstrate that the phosphatase-1 cofactor, growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a), an important component of the unfolded protein response (UPR), is absolutely required for type I-IFN and IL-6 production by mouse embryonic fibroblasts (MEFs) in response to dsRNA. GADD34 expression in MEFs is dependent on PKR activation, linking cytosolic microbial sensing with the ATF4 branch of the UPR. The importance of this link for anti-viral immunity is underlined by the extreme susceptibility of GADD34-deficient fibroblasts and neonate mice to Chikungunya virus infection

Long-term monitoring of the ANTARES optical module efficiencies using K-40 decays in sea water

[EN] Cherenkov light induced by radioactive decay products is one of the major sources of background light for deep-sea neutrino telescopes such as ANTARES. These decays are at the same time a powerful calibration source. Using data collected by the ANTARES neutrino telescope from mid 2008 to 2017, the time evolution of the photon detection ef¿ciency of optical modules is studied. A modest loss of only 20% in 9 years is observed. The relative time calibration between adjacent modules is derived as well.Albert, A.; Andre, M.; Anghinolfi, M.; Anton, G.; Ardid Ramírez, M.; Aubert, J.; Aublin, J.... (2018). Long-term monitoring of the ANTARES optical module efficiencies using K-40 decays in sea water. The European Physical Journal C. 78(8):1-8. https://doi.org/10.1140/epjc/s10052-018-6132-2S18788M. Ageron et al., ANTARES: The first undersea neutrino telescope. Nuclear Instruments and Methods in Physics Research A 656, 11–38 (2011)A. Albert et al., First all-flavor neutrino pointlike source search with the ANTARES neutrino telescope. Physical Review D 96, 082001 (2017)A. Albert et al., All-flavor Search for a Diffuse Flux of Cosmic Neutrinos with Nine Years of ANTARES Data. The Astrophysical Journal Letters 853, L7 (2018)B.P. Abbott et al., Multi-messenger Observations of a Binary Neutron Star Merger. The Astrophysical Journal Letters 848, L12 (2017)S. Adrián-Martínez et al., Measurement of atmospheric neutrino oscillations with the ANTARES neutrino telescope. Physics Letters B 714, 224–230 (2012)A. Albert et al., Search for relativistic magnetic monopoles with five years of the ANTARES detector data. Journal of High Energy Physics 7, 54 (2017)S. Adrián-Martínez et al., Limits on dark matter annihilation in the sun using the ANTARES neutrino telescope. Physics Letters B 759, 69–74 (2016)A. Albert et al., Results from the search for dark matter in the Milky Way with 9 years of data of the ANTARES neutrino telescope. Physics Letters B 769, 249–254 (2017)M.G. Aartsen et al., The IceCube Neutrino Observatory: instrumentation and online systems. Journal of Instrumentation 12, P03012 (2017)K. Abe et al., Calibration of the Super-Kamiokande detector. Nuclear Instruments and Methods in Physics Research A 737, 253–272 (2014)P. Amram et al., The ANTARES optical module. Nuclear Instruments and Methods in Physics Research A 484, 369–383 (2002)S. Adrián-Martínez et al., The positioning system of the ANTARES Neutrino Telescope. Journal of Instrumentation 7, T08002 (2012)J.A. Aguilar et al., Performance of the front-end electronics of the ANTARES neutrino telescope. Nuclear Instruments and Methods in Physics Research A 622, 59–73 (2010)J.A. Aguilar et al., The data acquisition system for the ANTARES neutrino telescope. Nuclear Instruments and Methods in Physics Research A 570, 107–116 (2007)J.A. Aguilar et al., Measurement of the atmospheric muon flux with a 4 GeV threshold in the ANTARES neutrino telescope. Astroparticle Physics 33, 86–90 (2010)J.A. Aguilar et al., Transmission of light in deep sea water at the site of the ANTARES neutrino telescope. Astroparticle Physics 23, 131–155 (2005)S. Kim et al., PubChem Substance and Compound databases. Nucleic Acids Research 44, 1202–13 (2016)G. Audi et al., The NUBASE evaluation of nuclear and decay properties. Nuclear Physics A 729, 3–128 (2003)J. Floor Anthoni. The chemical composition of seawater. http://www.seafriends.org.nz/oceano/seawater.htmJ.R. De Laeter et al., Atomic Weights of the Elements: Review 2000 (IUPAC Technical Report). Pure Applied Chemistry 75, 683–800 (2003)P. Amram et al., Background light in potential sites for the ANTARES undersea neutrino telescope. Astroparticle Physics 13, 127–136 (2000)C. Tamburini et al., Deep-sea bioluminescence blooms after dense water formation at the ocean surface. PLOS ONE, 8(7), (2013)J.A. Aguilar et al., Time calibration of the ANTARES neutrino telescope. Astroparticle Physics 34, 539–549 (2011)M. Ageron et al., The ANTARES optical beacon system. Nuclear Instruments and Methods in Physics Research A 578, 498–509 (2007)S. Adrián-Martínez et al., Time calibration with atmospheric muon tracks in the ANTARES neutrino telescope. Astroparticle Physics 78, 43–51 (2016)S. Adrián-Martínez et al., Letter of Intent for KM3NeT 2.0. Journal of Physics G. Nuclear Physics 43(8), 084001 (2016