Project Summary/Abstract The novel coronavirus that emerged in late 2019, termed SARS-CoV-2, quickly spread throughout the world and has, to date, infected millions and killed hundreds of thousands. This virus is shockingly complex in that the majority of infected individuals show few overt symptoms (though some data suggest they may have lasting damage nonetheless) but are largely healthy. In contrast, a small fraction of infected individuals exhibit a range of serious symptoms including pneumonia, acute respiratory distress, clotting disorders, and even death. The mechanisms that underly mild versus severe symptoms are not fully understood but immune mechanisms appear to play a role. Thus, we need to understand the roles of particular immune cells in order to understand the disease and properly treat it. Of particular interest is the role of CD8 T cells (CTL) in disease outcome. In this project we will use the rhesus macaque model of SARS-CoV-2 infection to assess the importance of CTL and other CD8+ cells in disease. In aim 1, we will deplete animals of all cells that express the CD8a molecule, including CTL and NK cells, and assess their ability to clear the virus. In aim 2, we will target only CTL for depletion and likewise assess their importance. In aim 3, we will use cells in the lab to assess how CTL interact with virus infected cells. Together, this project will comprehensively assess the importance of CTL in COVID-19 disease or protection from it.