Understanding the role of liquid “organelles” in influenza viral zoonotic spillover

We recently identified that human IAV exploits cellular processes to create sites specialised for genome assembly. These sites, named IAV inclusions, behave like the liquid organelles shown to arise by liquid-liquid phase separation, in which material properties are critical for efficient viral replication. Here we propose to investigate whether the formation and properties of IAV inclusions are conserved amongst IAVs adapted to different host species, and whether these sites facilitate genetic mixing between animal and human IAVs. This is a novel paradigm that explores the conceptual framework of phase separation in driving genetic mixing, viral evolution and IAV host spillover. This project will bring a deeper understanding to IAV zoonoses and may be of relevance to other zoonoses involving phase separated phenomena. These new concepts should provide opportunities for breakthroughs in influenza research at a fundamental level that could be the basis for applied interventions to control IAV zoonoses.