City (Work Address)
State/Province/County (Work Address)
Taylor Caddell is a second year MSc student in the McCormick lab at Dalhousie University. Her research focuses on understanding the role of the ATF6 branch of the unfolded protein response during coronavirus infection. Recently she has also been interested in investigating how coronavirus assembly affects host processes at the ER-Golgi intermediate compartment (ERGIC). She plans to transfer to the PhD program this summer to further her studies. Outside of the lab Taylor enjoys promoting science communication, being involved in the graduate student community, and coaching volleyball at a local volleyball club.
SARS-CoV-2 Membrane and Envelope proteins inhibit Spike-mediated activation of ATF6
Coronaviruses assemble at the ER-Golgi intermediate compartment (ERGIC). As its name suggests, the ERGIC participates in bidirectional vesicular traffic between the ER and Golgi. It is also a central hub for signaling pathways that traverse the secretory pathway and plays important roles in stress signaling, cholesterol regulation, interferon production, and inflammasome assembly. However, it is unknown how coronavirus assembly at the ERGIC affects these signaling pathways. Investigating the structural proteins of SARS-CoV-2, we found Spike selectively activates ATF6, an ER resident stress-sensing protein. However, the SARS-CoV-2 membrane (M) and envelope (E) proteins both inhibit Spike-mediated ATF6 activation. We observed ATF6 is not activated during human coronavirus hCoV-OC43 infection, suggesting that M and/or E may prevent Spike-mediated ATF6 activation during infection. Chemical activation of ATF6 with AA147 reduced replication of human coronaviruses hCoV-OC43 and hCoV-229E. By studying interactions between CoV structural proteins and host signaling proteins at the ERGIC, we hope to better understand how CoV replication impacts host cell physiology and responses to infection. Many current SARS-CoV-2 vaccines direct Spike expression in the absence of other structural proteins like E and M. Based on our findings, we expect that vaccine-mediated Spike expression may activate ATF6, which might be important for generating robust antiviral immune responses. As next generation vaccines incorporate other CoV structural proteins, it will be important to determine how they affect Spike antigenicity, which could be influenced by multiple host signaling pathways that traverse the ERGIC.