3-5-2- Toll-like receptor signaling
Although no TLR has been directly implicated in the recognition of SARS-CoV, the TLR family can recognize viral PAMPs. On the surface of cells, TLR1, TLR2, TLR4, and TLR6 have been implicated in the recognition of PAMPs from other viruses, while the endosomal receptors TLR3, TLR7, TLR8, and TLR9 detect viral nucleic acid PAMPs. Transcription of TLRs increases in mice following infection with MA15-SARS-CoV and in human DCs infected with SARS-CoV (Law et al., 2009; Zornetzer et al., 2010). Meanwhile, the spike protein of MERS-CoV triggers the expression of some negative regulators of the TLR signaling pathways. This induction subsequently results in the expression of both IL-1R-associated kinase (IRAK-M) and peroxisome proliferator-activated receptor-γ (PPAR), which are negative regulators of IRF7, a transcription factor that induces the expression of IFN-α and IFN-β (Al-Qahtani et al., 2017). Understanding the TLR signaling pathways in the context of MERS-CoV infection will contribute to controlling the viral infection, thereby mitigating the risk of its spread (Mubarak, Alturaiki, & Hemida, 2019). In addition to ssRNA recognition by TLR7 or TLR8 and potentially RIG-I, ssRNA viruses, like CoVs, can form dsRNA during their replication, which can be detected by TLR3 in the endosome (Bouvet et al., 2010; Hackbart, Deng, & Baker, 2020; K. A. Ivanov et al., 2004).