Human rhinovirus promotes STING trafficking to replication organelles to promote viral replication
Martha Triantafilou, Joshi M. Ramanjulu, Lee M. Booty, Gisela Jimenez‐Duran, Hakan Keles, Ken Saunders, Neysa Nevins, Emma Koppe, Louise K. Modis, G. Scott Pesiridis, John Bertin, Kathy Triantafilou
Abstract
Abstract Human rhinovirus (HRV), like coronavirus (HCoV), are positive-strand RNA viruses that cause both upper and lower respiratory tract illness, with their replication facilitated by concentrating RNA-synthesizing machinery in intracellular compartments made of modified host membranes, referred to as replication organelles (ROs). Here we report a non-canonical, essential function for stimulator of interferon genes (STING) during HRV infections. While the canonical function of STING is to detect cytosolic DNA and activate inflammatory responses, HRV infection triggers the release of STIM1-bound STING in the ER by lowering Ca 2+ , thereby allowing STING to interact with phosphatidylinositol 4-phosphate (PI4P) and traffic to ROs to facilitates viral replication and transmission via autophagy. Our results thus hint a critical function of STING in HRV viral replication and transmission, with possible implications for other RO-mediated RNA viruses.