Using nanoSIMS to study virus structure

Because of their size, lack of symmetry, structural heterogeneity, and high molecular weight, most large animal and human viruses are not amenable to typical analytical techniques, such as x-ray crystallography, nuclear magnetic resonance analyses, or fine-scale reconstruction by cryo-electron microscopy. In a recently published paper in Analytical Chemistry, NACS and BBTD scientists, together with University of Florida researchers, investigated the potential to use nanometer-scale secondary ion mass spectrometry (nanoSIMS) depth profiling to characterize the internal structure of the Vaccinia virion, a large and complex pox virus about 350 nanometers in length. Combining nanoSIMS, atomic force microscopy, and stable isotope labeling of virus DNA, the team documented a 100-fold change in virion erosion rate during nanoSIMS depth profiling and then developed a nonlinear, nonequilibrium model to correct the isotope depth profile data, reproducing the expected location of the DNA in the virion structure. This work demonstrated approximately 15-nanometer depth resolution in virions and provides an important reference for the analysis of viruses and phage in environmental samples.

This research was supported by the Laboratory Directed Research and Development Program (11-ERD-027).

[S.D. Gates, R.C. Condit, N. Moussatche, B.J. Stewart, A.J. Malkin, and P.K. Weber, High Initial Sputter Rate Found for Vaccinia Virions Using Isotopic Labeling, NanoSIMS, and AFM, Analytical Chemistry 90 (3), 1613 (2018), doi: 10.1021/acs.analchem.7b02786.]