Mass spectrometry imaging (MSI) is a label-free molecular imaging technique allowing an untargeted detection of a broad range of biomolecules and
xenobiotics. MSI enables imaging of the spatial distribution of
proteins,
peptides,
lipids and metabolites from a wide range of samples. To date, this technique is commonly applied to tissue sections in
cancer diagnostics and
biomarker development, but also molecular histology in general. Advances in the methodology and bioinformatics improved the resolution of MS images below the single cell level and increased the flexibility of the workflow. However, MSI-based research in virology is just starting to gain momentum and its full potential has not been exploited yet. In this review, we discuss the main applications of MSI in virology. We review important aspects of matrix-assisted
laser desorption/ionization (MALDI) MSI, the most widely used MSI technique in virology. In addition, we summarize relevant literature on MSI studies that aim to unravel virus-host interactions and virus pathogenesis, to elucidate
antiviral drug kinetics and to improve current
viral disease diagnostics. Collectively, these studies strongly improve our general understanding of virus-induced changes in the
proteome, metabolome and metabolite distribution in host tissues of humans, animals and plants upon
infection. Furthermore, latest MSI research provided important insights into the drug distribution and distribution kinetics, especially in antiretroviral research. Finally, MSI-based investigations of oncogenic viruses greatly increased our knowledge on
tumor mass signatures and facilitated the identification of
cancer biomarkers.