RT Journal Article
SR Electronic
T1 Structural landscape of the Respiratory Syncytial Virus nucleocapsids
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.02.14.528440
DO 10.1101/2023.02.14.528440
A1 Lorène Gonnin
A1 Ambroise Desfosses
A1 Maria Bacia-Verloop
A1 Didier Chevret
A1 Marie Galloux
A1 Jean-François Éléouët
A1 Irina Gutsche
YR 2023
UL http://biorxiv.org/content/early/2023/02/14/2023.02.14.528440.abstract
AB Human Respiratory Syncytial Virus (RSV) is a prevalent cause of severe respiratory infections in children and the elderly. The viral genome, enwrapped by the nucleoprotein N into a helical nucleocapsid (NC), is a template for the viral RNA synthesis and a scaffold for the virion assembly. Although the structures of NC filaments representative of the other major families of the Mononegavirales order have been solved, a detailed understanding of the RSV NCs is missing. This cryo-electron microscopy (cryo-EM) analysis highlights the polymorphism of the RSV nucleocapsid-like assemblies. We reveal in particular the non-canonical arrangement of the RSV NC helix, composed of 16 N per asymmetric unit, and the resulting systematic variations in the RNA accessibility. We demonstrate that this unique helical symmetry originates from recurring longitudinal interactions by the C-terminal arm of the RSV N, whose truncation abrogates the inter-turn contacts. We report the cryo-EM structures of the full-length helical NC filaments, double-headed NCs, ring-capped NCs and double-decameric N-RNA rings, as well as those of the alternative assemblies formed by a C-terminally truncated N mutant. In addition, we demonstrate the functional importance of the interface involved in the formation of the double-headed and the ring-capped interactions. We put all these findings in the context of the RSV RNA synthesis machinery and delineate the structural basis for its further investigation.Competing Interest StatementThe authors have declared no competing interest.