NSF Award
2027748
This research advances the national prosperity and the bioeconomy and enhances our understanding of the mechanisms that allow the spread of corona viruses between species. Results of this research may be the basis for identifying biomarkers of severity of disease or spread of SARS-CoV-2 (COVID-19 or COVID). This project will produce an understanding of why some coronavirus strains that normally infect specific animals (such as birds and bats) sometimes also infect humans, whereas other strains do not. This knowledge is critical for understanding how viruses break species barriers to colonize new hosts and precipitate widespread infections, as experienced during the ongoing COVID pandemic. Coronaviruses infect cells by binding to specific cell surface receptors and passing through organelles known as endosomes and lysosomes to access the cell interior. This project will investigate how the environment within these cellular structures regulates the intensity of viral infection. Through the use of comparative biology across different vertebrate species, the goal will be to identify conditions in endosomes and lysosomes that facilitate infection in particular organisms. This research may be the basis for identifying biomarkers of severity of disease or COVID spread. This research will also provide tools to enable a broad research community working on COVID and other viruses. This proposal also uses funding to train graduate and undergraduate students. As such this funding is training the next generation of leaders in science. Results expected from this work will facilitate identification and control of COVID spread in humans and other animals. <br/><br/>The coronoaviridae (CoVs) are a family of single-stranded RNA viruses that infect three vertebrate groups: mammals, birds and fish. Understanding the molecular determinants underpinning this tropism, namely why CoVs naturally and efficiently infect these species, and target specific tissues within these animals, is a fundamental biological concept. Definition of the mechanisms restricting CoV tropism is therefore critical for our understanding of how CoVs break species barriers and colonize new hosts. In this RAPID proposal, the role of the luminal microenvironment of the endolysosomal system in determining the efficiency of CoV infection will be studied for different CoVs in different vertebrate species. The central hypothesis is that the cellular proteins called ion channels resident in endosomes and lysosomes are differentially present in lower mammals and humans. Furthermore, these ion channels uniquely create environments within endosomes and lysosomes in lower mammals that are critical for supporting coronaviral infection and the differential expression of endolysosomal ion channels between tissues and species regulates the effectiveness of CoV infection. This hypothesis will be tested using a variety of cell models, imaging approaches and infection assays. This research is supported by the Symbiosis, Defense and Self-recognition program of the National Science Foundation.<br/><br/>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.
