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).