Final Report Summary - VIROPERO (TEMPORAL AND SPATIAL MODULATION OF ANTIVIRAL MAVS SIGNALING)
Our proposal aimed at understanding innate immune mechanisms that are taking places early upon virus infection, and more specifically, at determining how exactly viruses are recognized by the host cells. We are doing so by studying a panel of medically relevant viruses, mainly members of the Flavivirus family (Yellow fever virus, Dengue virus and the emerging Zika virus). Despite different tissue tropisms and disease outcome, these viruses cause illness whose severity is dictated by their ability to modulate the innate immune response. Our work should contribute to a better understanding of this response and lead to discoveries that will provide therapeutics to better combat these threatening human pathogens.
We started by studying the replication of Yellow fever virus (YFV) in a panel of human cells, including relevant immune cells such as plasmacytoid dendritic cells (pDCs). pDCs are the most important source of IFNs in response to virus infection We characterized the molecular mechanisms by which viral replication triggers pDCs-mediated antiviral immune responses. We have discovered that YFV is able to stimulate pDCs to produce antiviral cytokines by activating two distinct signaling pathways. Our results shed light on the level of plasticity and complexity of pDC-mediated viral sensing. These data were published in 2015 in the journal ‘Science Signaling’. Continuing using YFV as a model virus, we have highlighted that viral entry mechanisms dictate the magnitude of cytokine-mediated antiviral responses. These data were published in 2016 in the journal ‘mBio’. Works in progress include characterization of innate immune responses induced by Dengue and Zika viruses.
Besides these publications, the Marie Curie funding allowed me to gain independence. I was recently recognized as a ‘group leader’ by the Scientific board of my host institution, the Pasteur Institute in Paris. I was granted space and equipment to perform my research. In 2015, I was awarded the prestigious ‘EMBO Young Investigator prize’ that recognizes some of the best young group leader in Europe. I have been able to build a collaborative network, not only within the Pasteur Institute, but also at national and international levels. I have secured funding to manage a group of 6 people.
I believe that I am in a confortable position to continue investigating mechanisms underlying antiviral immune responses. The better we understand these mechanisms, the better we can develop strategies to fight viruses.