Biology subjects

Lamarre, A.

Publications and source records attributed to Lamarre, A..

2 recordsLinked to original sources

bioRxiv2024

The transcription factor IRF-5 is essential for the metabolic rewiring of CD8 T cells during chronic infection

Numerous transcription factors are involved in promoting an intricate gene expression program that leads to CD8 T cell exhaustion. Here, we found that the transcription factor IRF-5 is involved in limiting functional exhaustion of CD8 T cells by regulating the cell cycle and contributing to sustaining the mitochondrial functions and oxidative phosphorylation during the chronic stage of LCMV Cl13 infection. CD8 T cells lacking IRF-5 display reduced survival capacity and show increased signs of functional exhaustion during the chronic stage of infection. IRF-5-deficiency also resulted in a severely defective lipid metabolism, in a faulty mitochondrial envelope, and in the reduced capacity to produce ATP. Additionally, we observed increased lipid peroxidation in CD8 T cells lacking IRF-5, when compared with WT cells. These findings identify IRF-5 as a pivotal regulator of the metabolic rewiring that occurs in CD8 T cells during the chronic stages of infection and highlight its role in protecting cells from cell death, possibly by lipid peroxidation. SummaryIRF-5 is critical for regulating mitochondrial functions and oxidative phosphorylation in CD8 T cells during chronic stages of LCMV Cl13 infection.

immunology↗

bioRxiv2023

Flaviviruses alter endoplasmic reticulum-mitochondria contacts to regulate respiration and apoptosis

With no therapeutics available, there is an urgent need to better understand the pathogenesis of flaviviruses which constitute a threat to public health worldwide. During infection, dengue virus (DENV) and Zika virus (ZIKV), two flaviviruses induce alterations of mitochondria morphology to favor viral replication, suggesting a viral co-opting of mitochondria functions. Here, we performed an extensive transmission electron microscopy-based quantitative analysis to demonstrate that both DENV and ZIKV alter endoplasmic reticulum-mitochondria contacts (ERMC). This correlated at the molecular level with an impairment of ERMC tethering protein complexes located at the surface of both organelles. Furthermore, virus infection, as well as NS4B expression modulated the mitochondrial oxygen consumption rate. Consistently, metabolomic and mitoproteomic analyses revealed a decrease in the abundance of several metabolites of the Krebs cycle and changes in the stoichiometry of the electron transport chain. Most importantly, ERMC destabilization by protein knockdown increased virus replication while dampening ZIKV-induced apoptosis. Overall, our results support the notion that flaviviruses hijack ERMCs to generate a cytoplasmic environment beneficial for sustained and efficient replication.

microbiology↗