Single Cell Metabolomics: A Future Tool to Unmask Cellular Heterogeneity and Virus-Host Interaction in Context of Emerging Viral Diseases

Abstract

Viral emergence is an unpredictable but obvious event, particularly in the era of climate change and globalization. Efficient management of viral outbreaks depends on pre-existing knowledge and alertness. The potential hotspots of viral emergence often remain neglected and the information related to them is insufficient, particularly for emerging viruses. Viral replication and transmission rely upon usurping the host metabolic machineries. So altered host metabolic pathways can be exploited for containment of these viruses. Metabolomics provides the insight for tracing out such checkpoints. Consequently introspection of metabolic alteration at virus-host interface has evolved as prime area in current virology research. Chromatographic separation followed by mass spectrometry has been used as the predominant analytical platform in bulk of the analyses followed by nuclear magnetic resonance (NMR) and fluorescence based techniques. Although valuable information regarding viral replication and modulation of host metabolic pathways have been extracted but ambiguity often superseded the real events due to population effect over the infected cells. Exploration of cellular heterogeneity and differentiation of infected cells from the nearby healthy ones has become essential. Single cell metabolomics (SCM) emerges as necessity to explore such minute details. Mass spectrometry imaging (MSI) coupled with several soft ionization techniques such as electrospray ionization (ESI), laser ablation electrospray ionization (LAESI), matrix assisted laser desorption/ionization (MALDI), matrix-free laser desorption ionization (LDI) have evolved as the best suited platforms for SCM analyses. The potential of SCM has already been exploited to resolve several biological conundrums. Thus SCM is knocking at the door of virus-host interface.

Keywords: emerging viruses; imaging; mass spectrometry; single cell metabolomics; virus-host interaction.

FIGURE 1

Schematic diagram of virus-host interaction, single cell isolation and single cell metabolomics analysis. (A) Virus infecting the host cell, (B) virus-macrophage interaction, (C) virus encounters immune cell, (D) virus-host cell interaction, (E) metabolic changes at sub-cellular level, (F) Single cell isolation by laser microdisection, (G) microfluidic chip for single cell isolation, (H) fluorescence based cell sorting, and (I) mass spectrometry for single cell metabolomics analysis.