Determining the spatial-temporal and transcriptomic host response to emerging RNA viruses at a single cell resolution

National Institute Of Allergy And Infectious Diseases

Investigators

Abstract

Zoonotic disease spillovers effect human health on a global scale. Often, the pathogenesis associated with infection does not result only from direct action of the pathogen but arises through dysregulation of the immune response. Ameliorating the pathogenetic propensities of the virus and developing new antivirals or immune modulators requires detailed knowledge of how the host is responding to the infection and how the infectious agent is counteracting the host response. To accelerate this process, in vivo studies of complex host-pathogen interactions that are spatially, transcriptomically, and temporally resolved are needed. An in vivo integrated-omic approach that combines measurement of spatial and transcriptomic cell states over time with computational skills can identify important components of host responses that cannot be observed in vitro. This then allows for testable hypothesis generation in a more targeted manner to decrease the time to therapeutic discovery. Current technologies in single-cell RNA sequencing (scRNA-Seq) and high content tissue (HCT) imaging provide these types of data but are currently difficult to apply to emerging diseases due to requiring work in BSL-3/4 settings. Additionally, new computational pipelines are needed to integrate outputs of the multiple methods to create a picture of the full immune response. In this work, we aim to understand the complexities of the tissue specific immune response to VSV and EBOV during the early time of the infection by using a combined scRNA-Seq and HCT imaging approach.