Figure 1

Figure 1. From: Making Sense of Viral RNA Sensing.

Immune responses to foreign RNA. (a) The DDX1-DDX21-DHX36 helicase complex is a cytosolic sensor of viral RNA (symbolized here by the viral RNA mimetic polyI:C) in myeloid dendritic cells.2 DDX1 binds short and long polyI:C, whereas DDX21 and DHX36 bind to TRIF. The helicase complex is bound to TRIF in steady state and relocates to the mitochondria following polyI:C sensing. The helicase complex, together with MDA-5 and RIG-I, converges to IPS-1 for downstream activation of the transcription factors IRF3 and NF-κB. This results in the induction of proinflammatory cytokines (e.g., tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12)) and antiviral cytokines such as type I interferons (IFNs). These three cytosolic RNA sensors complement the activity of Toll-like receptor 3 (TLR3), which detects phagocytosed endosomal viral RNA and signals through TRIF, TAK1, and TRAF3. (b) The antiviral adaptive immune response to mouse mammary tumor virus (MMTV) and murine leukemia virus (MuLV) retroviruses relies on TLR7 activation in the mouse.3 Neutralizing antiviral antibody production necessitates viral uptake and TLR7 activation, but not viral replication, following intraperitoneal injection of retroviruses in I/LnJ mice. Phagocytosed viral RNA detected by endosomal TLR7 results in innate immune activation and cytokine production, but antiviral antibody response does not rely on antiviral type I IFN production.

Michael P Gantier, et al. Mol Ther. 2011 September;19(9):1578-1581.

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