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

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

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

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

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

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

Antiviral Res 2020
Participants
Input
Output
Participates
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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