Visualizing a viral genome with contrast variation small angle x-ray scattering.

Despite the threat to human health posed by some single stranded RNA viruses, little is understood about their assembly. The goal of this work is to introduce a new tool for watching an RNA genome direct its own packaging and encapsidation by proteins. Contrast Variation Small Angle X-Ray Scattering (CV-SAXS) is a powerful tool with the potential to monitor the changing structure of a viral RNA through this assembly process. The proteins, through present, do not contribute to the measured signal. As a first step in assessing the feasibility of viral genome studies, the structure of encapsidated MS2 RNA was exclusively detected with CV-SAXS and compared with a structure derived from asymmetric cryoEM reconstructions. Additional comparisons with free RNA highlight the significant structural rearrangements induced by capsid proteins, and invite the application of time-resolved CV-SAXS to reveal interactions that result in efficient viral assembly.