RSV ssRNA binds C-ter TLR7 dimer

Stable Identifier
R-HSA-9836773
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Human respiratory syncytial virus A
Compartment
endosome membrane, endosome lumen
ReviewStatus
5/5
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RSV ssRNA binds C-ter TLR7 dimer
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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.

Literature References
PubMed ID Title Journal Year
15827165 Inhibition of toll-like receptor 7- and 9-mediated alpha/beta interferon production in human plasmacytoid dendritic cells by respiratory syncytial virus and measles virus

Schlender, J, Hornung, V, Finke, S, Günthner-Biller, M, Marozin, S, Brzózka, K, Moghim, S, Endres, S, Hartmann, G, Conzelmann, KK

J Virol 2005
14976261 Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA

Diebold, SS, Kaisho, T, Hemmi, H, Akira, S, Reis e Sousa, C

Science 2004
32387475 Imiquimod suppresses respiratory syncytial virus (RSV) replication via PKA pathway and reduces RSV induced-inflammation and viral load in mice lungs

Salinas, FM, Nebreda, AD, Vázquez, L, Gentilini, MV, Marini, V, Benedetti, M, Nabaes Jodar, MS, Viegas, M, Shayo, C, Bueno, CA

Antiviral Res 2020
Participants
Input
Output
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as an event of
This event is regulated
Negatively by
Regulator
C-ter TLR7 dimer:HCQ [endosome membrane] (Homo sapiens)
Authored
Shamovsky, V  (2023-06-02)
Reviewed
Bergeron, HC  (2023-11-03)
Created
Shamovsky, V  (2023-06-02)
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