Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I-mediated immunity. (January 2018)

• Record Type: Journal Article
• Authors: Chiang, Jessica; Sparrer, Konstantin; van Gent, Michiel; Lässig, Charlotte; Huang, Teng; Osterrieder, Nikolaus; Hopfner, Karl-Peter; Gack, Michaela
• Is Part Of: Nature immunology. Volume 19:Number 1(2018)
• Page Start: 53
• Page End: 62
• Publication Date: 2018-01
• Subjects: Immunology -- Periodicals; 571.9605
• DOI: 10.1038/s41590-017-0005-y
• Languages: English
• ISSNs: 1529-2908

Abstract

Abstract The sensor RIG-I detects double-stranded RNA derived from RNA viruses. Although RIG-I is also known to have a role in the antiviral response to DNA viruses, physiological RNA species recognized by RIG-I during infection with a DNA virus are largely unknown. Using next-generation RNA sequencing (RNAseq), we found that host-derived RNAs, most prominently 5S ribosomal RNA pseudogene 141 (RNA5SP141 ), bound to RIG-I during infection with herpes simplex virus 1 (HSV-1). Infection with HSV-1 induced relocalization ofRNA5SP141 from the nucleus to the cytoplasm, and virus-induced shutoff of host protein synthesis downregulated the abundance ofRNA5SP141 -interacting proteins, which allowedRNA5SP141 to bind RIG-I and induce the expression of type I interferons. Silencing ofRNA5SP141 strongly dampened the antiviral response to HSV-1 and the related virus Epstein-Barr virus (EBV), as well as influenza A virus (IAV). Our findings reveal that antiviral immunity can be triggered by host RNAs that are unshielded following depletion of their respective binding proteins by the virus. RIG-I is a cytosolic RNA sensor. Gack and colleagues show that herpesviruses, duplex DNA viruses, also activate RIG-I by inducing cytoplasmic translocation and unmasking of an endogenous host 5S ribosomal pseudogene RNA, RNA5SP141 .