BBB Seminar - Irina Gutsche

Irina Gutsche
Institut de Biology Structurale, Grenoble, France

Respiratory syncytial virus (RSV) is the leading cause of child bronchiolitis and pneumonia, with a burden on the elderly comparable to that of influenza. Although prophylactic options such as vaccines and monoclonal antibodies have recently become available, no direct-acting RSV antiviral exists to date. Replication and transcription of RSV genetic material are critical steps for establishing and spreading infection, making them attractive therapeutic targets. These functions take place inside cytoplasmic membranelles biocondensates called viral factories and are carried out by the viral ribonucleoprotein particles, composed of the viral genomic RNA enwrapped by the viral nucleoprotein into a helical nucleocapsid and the RNA-dependent RNA polymerase complex. In this talk, we will dive into the structural landscape of the RSV nucleocapsids and explore the molecular mechanisms and extent of their polymorphism using single particle cryo-electron microscopy. We will also see how a single mutation that mimics a post-translational modification of the nucleocapsid we have recently identified in RSV infected cells can dramatically affect nucleocapsid properties. In addition, we will have a first glimpse into the structures and the spatial organization of the nucleocapsids within the viral factories of RSV-infected cells using cryo-electron tomography. This ongoing work marks a new step towards elucidating the structural origins and the functional implications of the non-canonical helical symmetry of RSV nucleocapsids. We hope that it will serve as a foundation for investigating dynamic conformational changes of the RSV RNA transcription and replication machinery in action. But for now, every new structure we solve raises more questions than it answers, making us realize that we are only scratching the surface and that fully understanding the molecular mechanisms of RSV genome synthesis is still a long way off.

Chairperson: Inari Kursula, Department of Biomedicine