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.