RNase L Activates the NLRP3 Inflammasome during Viral Infections

Chakrabarti, A., et al. Cell Host Microbe, 2015. 8;17(4):466-77.

Speaker: Wei-Ren Cheng (鄭惟仁)                              Time: 14:10~15:00, Jun 8, 2016

Commentator: Dr. Yao Chang (張堯 老師)         Place: Room 601

Abstract

The NOD-like receptor families are pattern recognition receptors that function in large molecular machines known as inflammasome. The NLRP3 inflammasome participates in many types of virus infection, including influenza A virus (IAV) [1]. During virus infection, RNase L, a common endoribonuclease for single-stranded RNA is activated and provides antiviral effects or regulates type I interferon signaling [2]. Until now, how viruses induce the activation of NLRP3 inflammasome remains unclear. The authors investigated the activation of NLRP3 inflammasome by RNase L. In vivo experiments showed that, in IAV-infected mice, RNase L not only improved the survival rate but provided antiviral effects. Using IAV or vesicular stomatitis virus to infect bone marrow-derived dendritic cells, data also indicated that the activation of NLRP3 inflammasome required RNase L and MAVS. To clarify the mechanism, the authors measured the importance of the enzymatic activities of RNase L. Results showed that the nuclease function of RNase L and cleaved RNA with 2’-3’-cyclic phosphate were necessary for NLRP3 activation in bone marrow-derived dendritic cells from mice and the human monocyte cell line, THP-1. DHX33, a cytosolic RNA sensor recently shown to activate NLRP3 can form a complex with NLRP3 and MAVS in response to RNase L-cleaved RNA with 2’-3’-cyclic phosphate. Taken together, the cleaved RNA products derived from RNase L can be sensed by DHX33 and lead to NLRP3 inflammasome activation during virus infection. This finding provides further investigation for the effect of RNase L on other types of inflammasome or additional co-factors that contribute to immune signaling pathway.

References:

1.    Allen, I.C., et al., The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity, 2009. 30(4): p. 556-65.

2.    Chakrabarti, A., B.K. Jha, and R.H. Silverman, New insights into the role of RNase L in innate immunity. J Interferon Cytokine Res, 2011. 31(1): p. 49-57.