Thomas Michiels

Major achievements

• Identification of an RNA replication signal (cis-acting replication element: CRE) in the coding region of cardiovirus genomes (Lobert et al., 1999 PNAS).
• IFN-lambda acts to protect epitheliums against viral infections (Sommereyns et al., 2008 PLoS Pathog.).
• Unrelated pathogens, including viruses and bacteria, use a common small linear motif (SLiM) to hijack cellular kinases of the RSK family (Sorgeloos et al., 2022 PNAS ; Lizcano-Perret et al., 2022 PLoS pathog.).

Question

How do viral proteins affect the signaling pathways in the host cell?

How do post-translational modifications such as phosphorylations, affect virus-host interactions?

Research focus

Thanks to their fast replication rate and the error-prone activity of their polymerases, RNA viruses are very fast-evolving organisms. They express proteins that are exquisitely adapted to target important hubs in the infected cell, to hijack signaling pathways, or to escape immune responses.

The VIRO lab is combining biochemical, molecular and cellular biology approaches to study how viral proteins interfere with host signaling and with the interferon response of the host.

Cardioviruses such as Theiler's virus (TMEV), Encephalomyocarditis virus (EMCV) or human Saffold virus (SAFV), express a very small protein called "leader" or "L". This protein hijacks cellular protein kinases of the RSK family and retargets theses kinases toward the nuclear pore complex thereby disrupting nucleocytoplasmic trafficking in the host cell. Current efforts aim to decipher the mechanisms and consequences of nucleocytoplasmic traffic perturbation, and, in a broader scope, to study how small linear motifs contained in viral proteins compete with cellular components to take the control of host cell pathways.

A related question addressed by the VIRO group concerns the link existing between RSK kinases and the antiviral kinase PKR, which is a well-known effector of the interferon (IFN-a/b or IFN-l) response. PKR inhibition by cardioviruses was shown to depend on the interaction between the leader protein and RSK kinases.

Some projects further assess the influence of viral and host protein phosphorylation on infection and host defenses.

Studying how viral proteins interfere with host functions not only contributes to the understanding of viral replication and pathogenesis but also contributes to unravel important cell biology mechanisms.

Projects

• Impact of viral protein phosphorylation on the replication of RNA viruses
• Analysis of PKR inhibition by viral proteins
• Modulation of RSK activity through protein-protein interaction
• Identification of Small Linear Motifs (SLiMs) contained in viral proteins, which hijack cellular kinases and thereby contribute to escape cellular responses.

Thomas Michiels graduated in Biology. Under the guidance of Professor Guy Cornélis, he discovered and characterized a new bacterial transposon, and obtained a PhD in Science from the university of Louvain (UCLouvain) in February 1988. He then contributed, still with Guy Cornélis, to the discovery of the type III secretion system in bacteria. With an EMBO long-term fellowship, he was introduced to the field of Virology, as a post-doc at the Pasteur Institute in Paris, in the laboratory of Prof. Michel Brahic. There, he started to work on the persistent infection of the central nervous system by Theiler's murine encephalomyelitis virus (Brahic, Bureau and Michiels, Annu. Rev. Microbiol. 2005).

Back to Brussels in 1993 as a Research Associate of the FNRS, he established a research group at the de Duve Institute of UCLouvain. With a title of full professor, he currently teaches general microbiology, molecular biology and virology. His group researches focus on the interactions between viruses and their host and recently unraveled a novel virulence mechanism shared by some viruses and bacteria. Thomas Michiels currently coordinates an EOS laboratory network on virology, co-funded by FWO and FNRS.