Seminar Abstract: Viruses have evolved many ways to evade innate immunity, and we can learn from them. Self-amplifying RNA (saRNA) is a promising vaccine platform, but the antiviral pathways triggered by double-stranded RNA limit its efficacy. We show that saRNAs are restricted by RNA interference in stem cells and by the kinase PKR in somatic cells. Cis-expression of the Nodamura virus B2 protein overcomes both barriers by sequestering replication-derived dsRNA, preventing translational shutdown without impairing interferon signalling or the self-adjuvant properties of saRNA. This suggests a strategy to improve saRNA efficacy while preserving its immunostimulatory potential. I will also show how the same principle can be applied to autoinflammatory disease, with the design of peptides based on viral antagonists that selectively block RNA sensors and dampen type I/III interferon-driven inflammation.

Biosketch: Dr Pierre Maillard is a UKRI Future Leaders Fellow and Senior Lecturer at the Blizard Institute, Queen Mary University of London (QMUL), where his group studies how cells combat viral infections with the long-term vision of developing innovative antiviral therapeutic strategies. He completed his PhD at the École Polytechnique Fédérale de Lausanne (EPFL), Switzerland, investigating cell-intrinsic defence mechanisms against retroviruses, before pursuing postdoctoral research at ETH Zürich, where he studied the antiviral role of RNA interference in mammals and subsequently at the Francis Crick Institute in London, exploring the interplay between antiviral RNA interference and the interferon system. In 2017, he was awarded a Wolfson UCL Excellence Fellowship to begin his independent research programme in the Division of Infection and Immunity at University College London and before establishing his group at QMUL’s Blizard Institute.