Primary Supervisor: Prof. F. van Kuppeveld, University of Utrecht, the Netherlands
Title: Stress granules as platform for antiviral signalling
Collaborators: Prof. M. Anthonsen, NTNU, Trondheim, Norway; Dr. R. Zahn, Janssen, Leiden, The Netherlands
Early Stage Researcher: Chiara Aloise
PROJECT DESCRIPTION:
Virus infection triggers several innate antiviral responses like the type I IFN and stress response pathway. Activation of the stress response pathway leads to inhibition of cellular translation and the formation of stress granules (SG), which have been proposed to function as a platform for viral RNA recognition. In addition, virus infection can turn on autophagy pathways and lead to changes in cellular metabolism. Most viruses have developed mechanisms to suppress IFN and stress response pathways and to redirect autophagy pathways and cellular metabolism for their own benefit. The aim of this study is to gain more insight how picorna- and coronaviruses, including SARS-CoV-2, antagonise IFN and stress response pathways and the proposed role of SGs in connecting these pathways. For the antagonistic mechanism, the possible role of the formation viral replication organelles (ROs) as a mean to hide viral RNA for cellular sensors will be investigated. Additionally, the role of autophagy, which has been implicated in RO formation, and metabolism changes for the viral life cycle of picorna- and coronaviruses, including SARS-CoV-2, will be evaluated. ESR4 will use the CRISPR/Cas9 technology to develop mammalian knockout cells (e.g. HeLa, Huh7) that are impaired in antiviral signalling pathways. The activation of specific antiviral signalling pathways in these cells will be compared to those in control cells, following infection or transfection of non-self RNA ligands. In collaboration with R. Zahn (Janssen), ESR4 will study whether co-expression of virus stress antagonists can enhance efficacy of specific vaccines. In collaboration with Prof. M. Anthonsen (NTNU), ESR4 will study the role of autophagy in the replication and dissemination of virus infection.
