Project #17962
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#17962 : Measles virus type 1 infection disturbs the mitochondrial network leading to type I interferon production through the RNA polymerase III/RIG-I pathway
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Name of Applicant : Jean-Pierre VARTANIAN
Date of application : 17-02-2022
Unit : Department of Virology
Location : Lwoff, second floor, room 207
Phone : +33 (0)1 44 38 94 45
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Project context and summary :

Measles virus (MeV) impairs the mitochondrial network. This leads to the fusion of mitochondria and simultaneous release of mitochondrial DNA (mtDNA). We have shown that released mtDNA is recognized as a danger signal, capable of stimulating signaling pathways and inducing the production of pro-inflammatory cytokines. The expression of human cytidine deaminase APOBEC3A is highly upregulated by interferon responses. This enzyme catalyzes the deamination of cytidine to uridine in single-stranded mitochondrial DNA substrates, resulting in the catabolism of edited DNA. Deep sequencing analyses of cytosolic mtDNA mutations revealed an APOBEC3A signature predominantly in the 5’TpCpG context. Using cell lines deprived of mtDNA, we have demonstrated the implication of mtDNA in the production of interferon and APOBEC3A expression during viral infection. We have shown that MeV induces mitochondrial network fragmentation and confirmed the implication of RNA polymerase III/RIG-I signaling in the capture of cytosolic mtDNA.

Related team publications :
Herpes Simplex Virus Type 1 Infection Disturbs the Mitochondrial Network, Leading to Type I Interferon Production through the RNA Polymerase III/RIG-I Pathway. Berry N, Suspène R, Caval V, Khalfi P, Beauclair G, Rigaud S, Blanc H, Vignuzzi M, Wain-Hobson S, Vartanian JP. mBio. 2021 Dec 21;12(6):e0255721. doi: 10.1128/mBio.02557-21. Epub 2021 Nov 23. PMID: 34809467
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Project Type : Medium
Status : Pending

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