Keynote Speaker -  Dr. Anand.

Virus breathing, metastability and epitope dynamics by integrative mass spectrometry and cryo-EM

RNA viruses are metastable macromolecular assemblies that respond to environmental changes through dynamic breathing motions. Cryo-Electron Microscopy and Amide hydrogen/exchange mass spectrometry (HDXMS) offer powerful insights  into dynamics of whole viral particles in solution. I will describe dynamics of  viral surface regions and core ribonucleoprotein in two model viruses: Dengue and Turnip Crinkle Virus (TCV). We have identified a broad neutralizing antibody, C10 that induces altered ‘breathing’ dynamics in dengue viral particles and shows unique stoichiometry-specific responses.  Deconvolution analysis of HDXMS has enabled us to identify residues on the surface that mediate altered interraft and intraraft interactions at different temperature perturbations and C10 stoichiometries. Cryo-EM of expanded TCV reveals strong interactions between the capsid proteins and the RNA genome correspond to asymmetric ribonucleoprotein core packing  observed near a unique 5-fold vertex in the expanded particle, which is the specific point of egress for the genomic RNA into the host. Our results highlight an active role of genomic RNA-protein core as environmental sensors and controlling capsid uncoating and RNA release inside hosts. A combination of HDXMS and cryo-EM has been invaluable in uncovering the significance of essential asymmetries in icosahedral virus assemblies. I will conclude my talk by sharing our insights into Spike dynamics across the SARS-CoV-2 variants and share perspectives on integration of biophysical insights of viruses with antibody recognition.

There will be additional 10 speakers