Endosomal recognition of single stranded (ss) RNA occurs by ...

created [InstanceEdit:9836770] Shamovsky, Veronica, 2023-06-02
dbId 9836737
displayName Endosomal recognition of single stranded (ss) RNA occurs by ...
literatureReference
modified [InstanceEdit:9838879] Shamovsky, Veronica, 2023-06-27
schemaClass Summation
text Endosomal recognition of single stranded (ss) RNA occurs by means of toll-like receptor 7 (TLR7) and TLR8 leading to induction of type I and type III interferons and proinflammatory cytokines via a MyD88-mediated signaling pathway (reviewed in Lester SN & Li K 2014; Tatematsu M et al. 2018). Viruses can enter mammalian cells using endosomal or phagosomal pathways delivering their genomes to endosomal compartments (reviewed by Cossart P & Helenius A 2014). For example, entry of respiratory syncytial virus (RSV), a (?)-sense ssRNA virus, occurs through clathrin-mediated endocytosis (Kolokoltsov AA et al. 2007; Krzyzaniak MA et al. 2013). Additionally, autophagy-dependent transfer of viral RNA products from the cytoplasmic viral replication sites into the endosome can trigger the TLR7/8-mediated immune responses (Lee HK et al. 2007). TLR7 likely plays a crucial role in the recognition of RSV. RSV infection upregulates TLR7 expression in human epithelial A549 cells (Dou Y et al. 2013; Sun T et al. 2018) and in the lung tissue of infected mice (Huang S et al. 2009; Lukacs NW et al. 2010). In the mouse model, the TLR7-MyD88 pathway has been found to be essential for the CD8+ T cell response, induction of type I interferon, and proinflammatory cytokines in mouse plasmacytoid dendritic cells (pDCs) during RSV infection (Davidson S et al. 2011; Kim TH et al. 2019). TLR7 or MyD88 deficiency in mice leads to a more severe RSV infection, characterized by mucus production, inflammation, and altered T cell responses with increased production of mucogenic cytokines (Rudd BD et al. 2007; Lukacs NW et al. 2010; Davidson S et al. 2011). Imiquimod, a TLR7 agonist, exhibits direct antiviral activity against RSV and modulates cytokine responses through the PKA pathway in human epithelial Hep-2 and A549 cells, suggesting that the drug may have therapeutic potential in controlling RSV pathogenesis (Salinas FM et al. 2020). Further, Schlender J et al. (2005) showed that RSV can inhibit type I interferon production in human pDCs stimulated with TLR7/9 agonists.

This Reactome event shows recognition of RSV ssRNA by TLR7 in the endosome lumen. However, the molecular mechanisms underlying activation/modulation of the TLR7 signaling pathway by RSV are not fully understood.

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