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Hélène Malet will present her work on the ”Structural and functional analysis of bunyavirus replication and transcription”, Thursday 1st of December 2022, at 1pm, Amphitheater G2, Université Claude Bernard Lyon 1, 50 Av Tony Garnier, 69007 Lyon.

 Host: Pierre-Yves Lozach (iWAYS-IVPC) 

The Bunyavirales is a very large order of segmented negative-stranded RNA viruses (sNSV). Among them, there are many human and animal pathogens against which no drug is currently available (Lassa, Hantaan, La Crosse viruses). In this context, we aim at understanding the mechanisms underlying two key steps of the viral cycle: replication and transcription of the viral genome. These processes are carried out by the viral polymerase that interacts with the RNA encapsidated by nucleoproteins.

To understand how nucleoproteins interact with each other to protect their RNA, I will describe the structure of the Hantaan nucleocapsid determined at 3 Å resolution by cryo-EM. I will present the cryo-EM structure of La Crosse virus polymerase that uncovers the organization of this essential enzyme. I will also show how replication and transcription assays coupled with high-resolution cryo-EM eventually led to the determination of 7 structures of La Crosse virus polymerase stalled at specific key active stages, revealing the large conformational changes that are necessary for activity.