A CRISPR screen identifies IFI6 as an ER-resident interferon effector that blocks flavivirus replication.

ABSTRACT: The endoplasmic reticulum (ER) is an architecturally diverse organelle that serves as a membrane source for the replication of multiple viruses. Flaviviruses, including yellow fever virus, West Nile virus, dengue virus and Zika virus, induce unique single-membrane ER invaginations that house the viral replication machinery¹. Whether this virus-induced ER remodelling is vulnerable to antiviral pathways is unknown. Here, we show that flavivirus replication at the ER is targeted by the interferon (IFN) response. Through genome-scale CRISPR screening, we uncovered an antiviral mechanism mediated by a functional gene pairing between IFI6 (encoding IFN-α-inducible protein 6), an IFN-stimulated gene cloned over 30 years ago², and HSPA5, which encodes the ER-resident heat sho

SUBMITTER: Richardson RB 

PROVIDER: S-EPMC6202210 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature