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

Abstract

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. Targeted MSI analysis of known lipid biomarkers across a viral plaqueWe focused on known lipid biomarkers for viral infection, which were shown to be remodelled during infection in previous liquid chromatography-MS (LC-MS) based lipidomics experiments that were performed in liquid cultures 8,37,38 . These lipid biomarkers are usually classified based on their chemical category, such as: glycerolipids (GLs), glycerophospholipids (GPs) and sphingolipids (SLs). Since the viral genome also encodes the biosynthetic pathway for SLs 32,33 , the lipids can also be classified based on their biosynthetic origin (i.e. produced by alga-or virusencoded enzymes). Additionally, these lipid biomarkers can be classified based on their relative abundance during infection (i.e. induction or reduction). Therefore, we grouped the lipids into three biological categories: virus-derived (encoded by the virus and induced during infection), host-induced and host-reduced (encoded by the host and induced or reduced during infection). vGSLs are the only virus-derived lipids known to date, with the majority of enzymes in their biosynthetic pathway encoded by the genome of the virus. vGSLs were found to be central components of the EhV membranes and to trigger host PCD during the lytic phase in a dose dependent manner [33][34][35] . Remodelled host lipids, on the other hand, include diverse classes: GLs such as BLL 36:6, TAG 48:1 and DGCC 40:7, and GPs such as PDPT 40:7 and PC 32:1, were all found to be induced during infection (i.e. 'host-induced'), while others, such as BLL 38:6, were found to be reduced (i.e. 'host-reduced') 8,37,38 . MS images of these lipid biomarkers across a plaque ( Figure 2) allowed us to ...

Paper Spray Ionization Ion Mobility Mass Spectrometry of Sebum Classifies Biomarker Classes for the Diagnosis of Parkinson’s Disease

“…In bloom-forming alga Emiliania huxleyi, unsupervised spatially aware clustering indicated a systemic metabolic shift toward lipids containing OCFA induced during viral infection . Similarly, a change in lipid metabolism is associated with disease phenotypes observed in a myriad of metabolomics studies from both plants and humans.…”

“…In bloom-forming alga Emiliania huxleyi , unsupervised spatially aware clustering indicated a systemic metabolic shift toward lipids containing OCFA induced during viral infection. 31 Similarly, a change in lipid metabolism is associated with disease phenotypes observed in a myriad of metabolomics studies from both plants and humans. Jenkins et al suggested an endogenous biosynthetic pathway in human plasma that results in the ratio of pentadecanoic acid (C15:0) to heptadecanoic acid (C17:0) as 1:2 instead of the expected 2:1 as seen in dairy fat.…”

Paper Spray Ionisation Ion Mobility Mass Spectrometry of Sebum Classifies Biomarker Classes for the Diagnosis of Parkinson’s Disease

“…30 In bloom-forming alga Emiliania huxleyi, unsupervised spatially-aware clustering indicated a systemic metabolic shift towards lipids containing OCFA induced during viral infection. 31 Similarly, a change in lipid metabolism is associated with disease phenotypes observed in a myriad of metabolomics studies from both plants and humans. Jenkins et al…”