Single-stranded RNA (ssRNA) has been identified as the natural ligand of TLR7 and TLR8 [1, 2].
ssRNA derived from HIV-1 or the influenza virus were shown to induce the production of proinflammatory cytokines in pDC [3, 4].
This induction was reproduced using polyU or GU-rich (ssRNA40) ORNs complexed with cationic lipids to protect them from degradation.
Upon stimulation with ssRNA, murine TLR7 and human TLR8 induced the activation of NF-κB, whereas human TLR7 and murine TLR8 failed, implying a species specificity difference in ssRNA recognition.
1. Diebold SS. et al., 2004. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science. 5;303(5663):1529-31
2. Heil F. et al., 2004. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science. 5;303(5663):1526-9.
3. Alter G. et al., 2007. Single-Stranded RNA Derived from HIV-1 Serves as a Potent Activator of NK Cells. J Immunol. 178:7658-7666.
4. Hornung V. et al., 2005. Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7.Nat Med. 11(3):263-70.