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


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 of RNA5SP141 from the nucleus to the cytoplasm, and virus-induced shutoff of host protein synthesis downregulated the abundance of RNA5SP141-interacting proteins, which allowed RNA5SP141 to bind RIG-I and induce the expression of type I interferons. Silencing of RNA5SP141 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.

SUBMITTER: Chiang JJ 

PROVIDER: S-EPMC5815369 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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

Chiang Jessica J JJ   Sparrer Konstantin M J KMJ   van Gent Michiel M   Lässig Charlotte C   Huang Teng T   Osterrieder Nikolaus N   Hopfner Karl-Peter KP   Gack Michaela U MU  

Nature immunology 20171127 1


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 re  ...[more]

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