Structure and assembly of respiratory syncytial virus
Primary Supervisor: Prof David Bhella, School of Infection and Immunity
Rotation Project:
Background: Respiratory syncytial virus is a leading cause of paediatric respiratory disease, causing bronchiolitis in neonates and infants. RSV is a negative-sense, single-stranded RNA containing enveloped virus and assembles filamentous virions at the host cell plasma membrane. We have recently published the intermediate resolution structure of the matrix protein (M) layer, which forms a helical lattice underneath the viral envelope and is critical in coordinating virion assembly. We also found that the viral glycoproteins (F and G) are helically ordered on the viral envelope, and that this is coordinated by the underlying M array.
Aim(s): In this project we will use cryogenic electron tomography to solve the high-resolution structure of the M-layer, with the aim of resolving the molecular contacts between M and F/G. We will also use tomography to image the site of virion assembly, to understand how alternate packing of M and F/G may define virion structure and assembly.
Training outcomes: The trainee will gain experience in virus culture, transmission electron microscopy, cryo-ET, 3D image reconstruction by sub-tomogram averaging and the construction of atomic models of protein structures.
References:
Conley, M. J. et al. (2022) Helical ordering of envelope associated proteins and glycoproteins in respiratory syncytial virus. EMBO Journal, 41(3), e109728. (doi: 10.15252/embj.2021109728) (PMID:34935163) (PMCID:PMC8804925)