Assessing the pro-viral role of STING in human rhinovirus infections

Abstract

Human rhinoviruses (HRVs) are the predominant cause of the common cold by infecting the upper respiratory tract and may lead to exacerbation of asthma and COPD. The human immune system has developed innate antiviral responses, including the cGAS-STING pathway, which recognizes cytosolic double-stranded DNA and leads to the expression of type I interferons. While STING expression appeared to inhibit the replication of a variety of viruses, it was shown to promote HRV replication. The mechanism contributing to the pro-viral role of STING in HRV infection remains unknown. Here we further elucidated the role of STING in HRV replication. We found that STING promoted HRV-A16 replication, but had no role in HRV-A2 and HRV-B14 replication. Furthermore, treatment with the STING antagonist H-151 did not affect HRV-A16 replication, whereas a STING autophagy mutant lowered its replication. We also isolated HRV-A16 strains that evolved to replicate independently of STING. Within these strains, missense mutations were found in the genes encoding the 2A and 2C proteins. Lastly, we aimed to establish fluorescently labelled human STING alongside a split fluorescent system for HRV-A16, to enable live cell imaging of their localization. Altogether, this report identified a crucial role for STING during HRV-A16 replication and a potential therapeutic target during HRV infections.