Bunyaviricetes is a large class of viruses that have a segmented negative stranded RNA genome. Divided into 15 families, this class contains major human pathogens, such as Lassa or Crimean Congo Hemorrhagic fever viruses that are considered as priority viruses by the World Health Organization due to their pathogenicity and the lack of available countermeasures. Other viruses of the Bunyaviricetes class are emerging, such as Hantaan virus, that causes hemorrhagic fever in humans, with 15% mortality rate. In this context, researchers from the Methods and Electron Microscopy Group are interested in Hantaan virus polymerase. This central enzyme is involved viral replication, which consists of producing copies of the genome, and transcription, which enables the synthesis of viral messenger RNA. In this study, they have used high-resolution cryo-electron microscopy to determine the entire structure of Hantaan polymerase, in the absence of RNA, in 3 distinct oligomeric states : monomer (250kDa), symmetric dimer (500kDa) and hexamer (1.5 MDa). These structures reveal the organization of each of the polymerase domains, in particular the cap-binding domain required for transcription initiation, and the C-terminal domain essential for dimerization. SEC-MALS and mass photometry analyses indicate a rapid equilibrium between these different oligomers. When viral RNA is added, this equilibrium is disrupted and another equilibrium appears between asymmetric monomers and dimers. These results suggest a stabilization and storage function for apo multimers, upstream of replication and transcription activities.
Structural characterization of the oligomerization of full-length Hantaan virus polymerase into symmetric dimers and hexamers. Durieux Trouilleton Q, Housset D, Tarillon P, Arragain B*, Malet H*. Nature communications 2024 ; 15(1):2256.
Contact : Hélène Malet, Methods and Electron Microscopy Group (IBS/MEM)