Name
Coronavirus membrane proteins disperse the trans-Golgi network and inhibit anterograde protein trafficking in the secretory pathway
Presenter
Craig McCormick, Dalhousie University
Co-Author(s)
Craig McCormick1, Taylor Caddell1, Rory P. Mulloy2, Jennifer Corcoran2, Eric Pringle1 1. Microbiology & Immunology, Dallhousie Univiersity, Halifax, NS, Canada. 2. Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, Canada.
Abstract Category
Building & Escaping
Abstract
Coronaviruses (CoVs) use the endoplasmic reticulum (ER) for synthesis and processing of viral transmembrane proteins, including those that sculpt ER membranes into replication compartments as well as structural proteins that participate in virus assembly. We determined that amongst these CoV proteins, Spike triggered ER stress and activated all three arms of the unfolded protein response (UPR). By contrast, Membrane (M) selectively inhibited the ATF6 arm of the UPR, as well as two other ER-localized sensor proteins, SREBP2 and STING; all three sensors require anterograde trafficking in the secretory pathway to elicit downstream transcriptional responses. We demonstrate that M accumulates with cholesterol at the cis-Golgi and inhibits anterograde trafficking from this site, while dispersing the trans-Golgi network (TGN). Because CoV egress does not require the distal secretory pathway, this mechanism could allow the virus to selectively interfere with host responses to infection without impeding egress of nascent virions.