Hybrid experimental‐mathematical methods for probing dynamic proteome organization during viral infections

Abstract

Every year, a major cause of human disease and death worldwide is infection with the various viral pathogens that are intrinsic to our ecosystem. The outcomes of viral infections derive from dynamic virus‐host cell interactions that function either in promoting virus replication or in host defense against invading pathogens. An essential component of these virus‐host interactions is spatial organization. Eukaryotic viruses replicate within highly organized host cells that compartmentalize their vast cellular proteomes within organelles. Alterations in organelle shape, composition, function, and dynamics are prominent features of virus replication cycles, although the knowledge of the mechanisms involved remains limited.This presentation will describe the integration of experimental studies, mathematical modeling and inference methods for understanding the dynamic regulation of organelles during viral infection. The experimental methods presented will include live‐cell microscopy and quantitative mass spectrometry‐based proteomics for characterizing both organelle changes and virus‐host protein interactions during the progression of an infection. These studies discovered 1) dynamic changes in organelle composition, 2) translocation of cellular proteins from one subcellular compartment to another, and 3) temporal virus‐host protein interactions within organelles that induce alterations in host biological pathways (Figure 1).The value of these integrative methods is demonstrated by the identification of mechanisms through which viruses remodel subcellular organelle function to suppress host defense and promote viral replication. Furthermore, our findings are starting to uncover how viruses regulate the dynamics of organelle biogenesis during infection. Overall, these studies highlight how integrative omic technologies can help paint a picture of the pathogen's life cycle and aid in the future development of antiviral therapies.Support or Funding InformationNIH grants GM114141 and HL127640, and Mallinckrodt Scholar AwardThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.