Principal Investigator Matthew Shoulders
Because the proteostasis network assists client proteins in attaining functional conformations, it is a primary determinant of the mutational landscape accessible to evolving proteins in biological settings (e.g., the work of Susan Lindquist, Dan Tawfik, and others). Of particular interest to our group, the rapid evolution of RNA viruses engenders high adaptability to environmental pressures (e.g., host immune systems). Understanding, predicting, and constraining RNA virus evolution requires a comprehensive picture of factors that define the accessible mutational landscape. Our data show that RNA viruses hijack host cell proteostasis mechanisms to assist the folding and trafficking of viral protein variants with sub-optimal biophysical properties, enabling more comprehensive exploration of the mutational landscape. The results are providing insight into systems beyond the HSP90 chaperone that is already known to have key roles in evolution.