RIG-I detects viral genomic RNA during negative-strand RNA virus infection

J. Rehwinkel et al., Cell 140, 397 (2010)

Speaker: Wan-Ying Lin (林宛瑩)                                  Time: 15:10~16:00, May 12, 2010

Commentator: Dr. Hsiao-Sheng Liu (劉校生老師)      Place: Room 601

Abstract:

During viral infection, innate immunity can be triggered by sensing viral nucleic acids. Distinct types of sensors were found to detect viral nucleic acids. Toll-like receptors (TLRs) senses viral DNA or RNA in endolysosomes. RIG-I-like receptors (RLRs) and DNA sensors recognize viral RNA and DNA in cytoplasm respectively. This surveillance leads to type I interferon (IFN) production essential for antiviral responses. RIG-I is responsible for many RNA viruses including influenza A virus, Sendai virus and Hepatitis C virus (1). RIG-I

-deficient mice are highly susceptible to infection with these viruses. Reports indicate that viral genomes, viral transcripts or replication intermediates, RNase L cleavage products of cellular RNA could trigger RIG-I. However, these studies were based on different biological system and without confirming the identity of synthetic RNAs (2). Thus the natural ligands to activate the RIG-I-mediated immunity have not been clarified. In this study, the authors used a mock infection system with reconstitution of viral ribonucleoprotein particles (vRNPs) of influenza A virus. RNAextracted from vRNP reconstitution induced the RIG-I-dependent IFN production. Lower viral RNA (vRNA) and complementary RNA (cRNA) but normal messenger RNA (mRNA) led to reduced IFN induction. So the authors suggest that transcription of viral genomes is dispensable for IFN production. 5’-triphosphate RNA, which was resistant to DNase and sensitive to RNase V1+A and phosphatase CIP, accounted for the stimulatory activity. Their results further showed that NS1 could interact with stimulatory RNA and RIG-I in a trimolecular complex. NS1-associated RNA was CIP sensitive and the size was corresponding to genome segment. The phenomenon of that viral genomic RNAs triggered RIG-I was also seen in Sendai virus infection. In sum, negative-stranded RNA viral genomes bearing a 5’-triphosphate group were natural ligands for RIG-I and can trigger cellular intrinsic innate immunity during viral infection. 

References:

1. M. Yoneyama et al., Nat Immunol 5, 730 (Jul, 2004).

2. M. Schlee et al., Immunol Rev 227, 66 (Jan, 2009).