Sensing of RNA viruses: a review of innate immune receptors involved in recognizing RNA virus invasion

Abstract

Our knowledge regarding the contribution of the innate immune system in recognizing and subsequently initiating a host response to an invasion of RNA virus has been rapidly growing over the last decade. Descriptions of the receptors involved and the molecular mechanisms they employ to sense viral pathogen-associated molecular patterns have emerged in great detail. This review presents an overview of our current knowledge regarding the receptors used to detect RNA virus invasion, the molecular structures these receptors sense, and the involved downstream signaling pathways.

Fig 1

Signaling cascade following TLR2/TLR4, TLR7/TLR8, and TLR3 activation with envelope glycoprotein, ssRNA, and dsRNA, respectively. MyD88 and TRIF are the adaptor proteins that initiate the different pathways activating IRF3, IRF7 (pDCs only), NF-κB, and AP-1 in order to induce the antiviral response. NF-κB and AP-1 combine to induce the transcription of inflammatory cytokines. IRF3/IRF7 in association with both NF-κB and AP-1 form the enhanceosome for the transcription of IFN-β/IFN-α, respectively. In addition, IRF7 also has some IFN-β-stimulatory effect (not shown in the figure). (…), pathway outlined elsewhere in the illustration.

Fig 2

Left half, signaling via IPS-1 following dsRNA/ssRNA recognition by RIG-I and MDA5. IPS-1 serves as a platform to coordinate the activation of two of the signaling pathways also utilized by the TLRs (cf. Fig. 1), that is, the activation of RIP1 for NF-κB nuclear translocation and the activation of IKKs for IRF3 phosphorylation and translocation, leading to the expression of proinflammatory cytokines and IFN-β, respectively. Right half, formation of inflammasomes by NLRP3. Inactive NLRP3 oligomerizes upon stimulation by an unknown mechanism. ASC becomes associated with the complex. This leads to the recruitment of procaspase-1, which dimerizes and autoactivates by proteolytic cleavage, generating active caspase-1. Caspase-1 mediates the activation of IL-18 and IL-1β from inactive pro-IL-18 and pro-IL-1β, respectively. (…), the continuation of this pathway is outlined in Fig. 1.