This research will provide increased knowledge of the molecular factors enabling different hosts (especially bats vs. humans) to tolerate the recently emergent SARS-Cov-2 coronavirus. This project will use bat cell line models to investigate differences in cellular proteins which lead to differences in immunity profiles of cells from the different species. The proposed research will identify proteins that are differentially active in different cell line models, and the effects that immune-stimulating factors and SARS-CoV-2 proteins have on host cell protein activities. Results from this research could lead to new insights into why and how certain viruses, in particular SARS-CoV-2, can be tolerated in some species (e.g., bats) but not others (e.g., humans), and could provide information for the emergence of future viruses that can cause pandemics in animal and human populations. The interdisciplinary research team comprises three experienced lead scientists with expertise in complementary areas of research. In addition, the research will provide training to two graduate students who will be able to pursue careers in related areas in academia, the private sector, or government.
The goal of this research is to further knowledge of the molecular processes that underlie species-specific infection of cells with SARS-CoV2. This research will provide insights into transcription factor-based differences between host cells of bat origin, which can tolerate SARS-CoV2 infection in a non-pathogenic manner, vs human and other bat cells that do not show this tolerance. The research involves the collaboration of three PIs with complementary approaches that they will bring to this project. Five major experimental goals will be addressed: 1) characterization of transcriptional and nuclear proteomic profiles that distinguish different bat cell lines; 2) use of a novel protein-binding microarray to profile active transcription factors among these cell lines; 3) characterization of candidate immunity transcription factors, such as NF-?B and IRFs, that are likely different between SARS-CoV2 tolerant and susceptible cell lines; 4) effects of SARS-CoV2 gene products on identified transcription factors in the various cell lines; and 5) potential for replication of novel SARS-CoV2 tracer viruses in different bat cell lines. The proposed research will increase knowledge of SARS-SoV-2 biology. In addition, it investigates the hypothesis that bat cells have evolved molecular immunity pathways that promote or lead towards tolerance (perhaps even symbiosis) of bats with coronaviruses. Such information may lead to the identification of therapeutics for humans and animals against coronaviruses. This RAPID award is made by the Physiological and Structural Systems Cluster in the BIO Division of Integrative Organismal Systems, using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
