MASS SPECTROMETRY IN VIROLOGICAL SCIENCES

Abstract

Virology, as a branch of the life sciences, discovered mass spectrometry (MS) to be the pivotal tool around two decades ago. The technique unveiled the complex network of interactions between the living world of pro- and eukaryotes and viruses, which delivered "a piece of bad news wrapped in protein" as defined by Peter Medawar, Nobel Prize Laureate, in 1960. However, MS is constantly evolving, and novel approaches allow for a better understanding of interactions in this micro- and nanoworld. Currently, we can investigate the interplay between the virus and the cell by analyzing proteomes, interactomes, virus-cell interactions, and search for the compounds that build viral structures. In addition, by using MS, it is possible to look at the cell from the broader perspective and determine the role of viral infection on the scale of the organism, for example, monitoring the crosstalk between infected tissues and the immune system. In such a way, MS became one of the major tools for the modern virology, allowing us to see the infection in the context of the whole cell or the organism. © 2019 John Wiley & Sons Ltd. Mass Spec Rev.

Keywords: GEMMA-MS; capsids; charge-detection mass spectrometry; viral infections.

Figure 1

CDMS histogram of bacteriophage P22 with a bin size of 168 kDa (left panel). In the spectrum, there is a procapsid shown at ca. 24 MDa, with a smaller peak at ca. 20 MDa attributed to empty capsids. The histogram was calculated based on charge‐to‐mass plot (right panel) where points in the charge range 300–350 represent mature capsids, while points in the charge range 400–450 represent procapsids with scaffold proteins, detached during capsid maturation (after Keifer et al., 2014). © 2014 John Wiley and Sons. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

Interaction between canine parvovirus capsids and a monoclonal antibody complexing viral capsids acquired using CDMS. On the following spectra (b–f), increasing concentrations of antibody and the same concentration of capsids are measured (after Dunbar et al., 2018). © 2018 American Chemical Society. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 3

nES‐GEMMA acquired spectra of EM diameters of: (a) cowpea mosaic virus, (b) West Chester norovirus, (c) phage P22, and (d) phage T5. Spectra were acquired based on three different concentrations of viral structures (colors on plots) (after Weiss et al., 2019). EM, electrical mobility. © 2019 The Authors, under the terms of the Creative Commons. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 4

Scheme of instruments using nanomechanical resonators for single particle mass sensing. SAWN or nanoESI sources generate a nebulized analyte, directing aerosol into a set of chambers where molecules are separated. Instead of charge, aerodynamic force is used for separation. Finally, molecules interact with nanomechanical resonators able to detect (resonate) only a defined MW range. The dimensions of resonators are width, 300 nm; thickness, 160 nm; and length, 7–10 μm. SAWN, surface acoustic wave nebulization. © from Dominiguez‐Medina et al., . Reprinted with permission from AAAS. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 5

The overview of the strategy of proteotyping the influenza. With permission from Downard (2013). © 2013 Royal Society of Chemistry. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 6

The workflow of RT‐PCR/ESI‐MS analysis. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 7

Schematic representation of NS5A binding proteins identified by TAP‐MS. © 2014 Elsevier. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 8

Interaction network of host‐viral proteins. © American Society for Biochemistry and Molecular Biology. [Color figure can be viewed at wileyonlinelibrary.com]