Fine-tuned regulation of viral protein interactions involved in the formation of respiratory syncytial virus viral factories
Marie GALLOUX - INRAE
Abstract : Respiratory syncytial virus (RSV) is the main cause of bronchiolitis and pneumonia in children and elderly people. During infection, the transcription and replication of the viral genome by the viral polymerase L take place within cytoplasmic viral factories. These are cytoplasmic membraneless organelles formed by liquid-liquid phase separation (LLPS) driven by the interactions between the viral nucleoprotein N, which encapsidates the viral genome, and the phosphoprotein P. RSV viral factories are also characterised by the presence of specific subcompartments where the viral transcription factor M2-1 and viral mRNA concentrate. These observations highlight the structural and functional complexity of these organelles, which is expected to depend on the precise regulation of protein-protein and protein-RNA interactions.
Among the mechanisms involved in these regulations, we have recently shown that post-translational modification events of the N protein can regulate its conformation, and indirectly influence LLPS. In parallel, to gain insights into the structural and functional complexity of RSV-induced LLPS, we investigated the roles of the viral proteins N, P and M2-1, and of the RNA involved in forming RSV pseudo-viral condensates in vitro, using the Phase Scan technique. Our results revealed the importance of the respective oligomeric state and subdomains of N and P for LLPS and demonstrate the active role of M2-1 in forming pseudo-viral condensates. This study paves the way for further investigation into events involved in the formation of subcompartments within RSV viral factories.
Contact: emmanuelle.quemin@i2bc.paris-saclay.fr
