Grant: Project Grant

Viruses infect all known forms of life, including single celled organisms such as bacteria and yeasts. While studies of viruses in bacteria have led to remarkable advances for basic research such as the discovery of CRISPR, single-celled eukaryotic organisms have been comparatively silent on this topic. We have discovered a new anti-viral mechanism in the budding yeast Saccharomyces cerevisiae. This mechanism employs a protein called Nuc1, which is homologous to endonuclease G (endoG), a protein family found in all eukaryotic organisms, and even in bacteria. Nuc1, like endoG, resides within the cells mitochondria, a known hub of viral innate immunity in humans. Through our studies of Nuc1, we have discovered that the yeast "L-A" virus causes lethal pathogenesis when it is left unchecked in cells lacking Nuc1. We have exploited this lethal consequence of the L-A virus to discover new factors controlling viral repression. Intriguingly, human homologs of some of these factors attenuate SARS-Cov-2, though their mechanism remains unknown. This work exploits the unparalleled power of yeast as an experimental model to investigate these new viral repression mechanisms.