\"In plaque-mass spectrometry imaging\" reveals a major metabolic shift towards odd-chain fatty acid lipids induced by host-virus interactions

Tapping into the metabolic cross-talk between a host and its virus can reveal unique strategies employed during infection. Viral infection is a dynamic process that generates an evolving metabolic landscape. Gaining a continuous view into the infection process is highly challenging and is limited by current metabolomics approaches, which typically measure the average of the entire population at various stages of infection. Here, we took a novel approach to study the metabolic basis of host-virus interactions between the bloom-forming alga Emiliania huxleyi and its specific virus. We combined a classical method in virology, plaque assay, with advanced mass spectrometry imaging (MSI), an approach we termed "in plaque-MSI". Taking advantage of the spatial characteristics of the plaque, we mapped the metabolic landscape induced during infection in a high spatiotemporal resolution, unfolding the infection process in a continuous manner. Further unsupervised spatially-aware clustering, combined with known lipid biomarkers, revealed a systematic metabolic shift towards lipids containing the odd-chain fatty acid pentadecanoic acid (C15:0) induced during infection. Applying "in plaque-MSI" might pave the way for the discovery of novel bioactive compounds that mediate the chemical arms race of host-virus interactions in diverse model systems.