Controlling Host Responses to Infection

Pathogen invasion of host cells causes a myriad of functional changes including alterations of chromatin accessibility often limiting defense responses, shunting of cellular resources to centers of viral replication, and rearrangement of intracellular membranes to facilitate genome reproduction and progeny release. Systems biology approaches provide global snapshots of pathogen induced changes following infection and provide a variety of tools to begin to define how cellular homeostasis is disrupted, but improvements on these tools are required to determine how cellular functions are altered post infection. Chromatin accessibility techniques, biochemical assays to assess the activity of epigenetic enzymes, scalable sample collection platforms, and activity-based probes were used to characterize how human respiratory viruses modify host responses in infected human lungs over time. These studies enhanced our knowledge of how pathogens usurp the host environment during infection and identify additional targets for future evaluations of medical countermeasures.. Authors: Mitchell, Hugh D. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)]; Krishnamoorthy, Sankarganesh [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)]; Anderton, Christopher R. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)]; Berger, Madelyn R. [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)]; Bhattacharjee, Arunima [Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)]. DOE Contract: AC05-76RL01830. Subjects: 59 BASIC BIOLOGICAL SCIENCES; affinity-based probe; ATAC-Seq; chromatin accessibility; virus