Project title: The functional interplay between flaviviruses and mitochondria
Project description: Infections with flaviviruses represent a major public health concern. For instance, dengue virus (DENV) causes the most prevalent arthropod-borne viral disease with an estimated 400 million individuals infected each year. More recently, the closely related Zika virus (ZIKV) emerged as a global priority since its infection can cause Guillain-Barré syndrome and a severe microcephaly in newborns while it is transmissible both sexually and congenitally in addition to infection by mosquito bites. Finally, West Nile virus (WNV) is endemic in Canada and potentially lethal. Unfortunately, no antiviral therapies are available against these viruses, partly because the mechanistic details of their respective life cycle and pathogenesis remain poorly understood. Hence, these viruses are of particular interest both at the fundamental and clinical levels.
With the aim to better understand the pathogeneses of DENV and ZIKV and to identify novel antiviral targets, the Chatel-Chaix lab’ focuses its research on discovering novel virus/host interactions engaged in the functional and morphological hijacking of specific cellular machineries by the viral replication factories. Notably, we have recently shown that DENV and ZIKV perturb the morphology of mitochondria which make physical contact with virus-induced endoplasmic reticulum-derived ultrastructures. This results in an alteration of their functions such as oxidative respiration, antiviral innate immunity and virus-induced apoptosis. Hence, we believe that this mitochondrial “reprogramming” contributes to generate a cytoplasmic environment which is favorable to virus replication. The proposed postdoctoral project aims at deciphering how mitochondrial processes are modulated and co-opted by flaviviruses notably through the analysis of proteome and metabolic activity of mitochondria during the infection. We also wish to extend our work to other flaviviruses such as West Nile virus as well as the betacoronavirus SARS-CoV-2, that will be manipulated in the biosafety level 3 facility of our research center.
Relevant publications: Mazeaud et al., Viruses, 2021; Anton et al., Cellular Microbiology, 2021; Kaptein et al., Nature 2021; Cortese et al., Cell Host & Microbe, 2020; Chatel-Chaix et al., Cell Host & Microbe, 2016.
The candidate must have a PhD degree, a strong publication record and a solid background in virology and cell biology. Experience in mitochondrial biology, mass spectrometry, biosafety level 3 work and/or in vivo murine models of infection will be considered as an asset.