病毒单链RNA的内体识别是通过toll样受体7 (TLR7)和TLR8实现的。TLR7和TLR8检测来自正粘病毒(甲型流感)、慢病毒(人类免疫缺陷病毒-1,HIV-1)、水疱病毒(水疱性口炎病毒，VSV)、肠道病毒(柯萨奇B病毒)、β冠状病毒(严重急性呼吸综合征相关冠状病毒1型，SARS-CoV-1)和黄病毒(HCV和西尼罗河病毒)(Hemmi H et al. 2002;Jurk M et al. 2002;Diebold SS et al. 2004;Heil F et al. 2004;塞万提斯-巴拉干等人2007;Li Y et al. 2013;Scheuplein VA等人2015;在Lester SN & Li K 2014年审查)。 Specifically, GU-rich ssRNA oligonucleotides derived from HIV-1, for example, stimulate dendritic cells (DC) and macrophages to secrete interferon-alpha and proinflammatory, as well as regulatory, cytokines (Heil F et al. 2004). This has been found to be mediated by TLR7, as well as TLR8. Similarly, SARS‑CoV‑1 ssRNAs induced mononuclear phagocytes to release considerable levels of pro‑inflammatory cytokines TNF‑a, IL‑6 and IL‑12 via TLR7 and TLR8 (Li Y et al. 2013). Bioinformatics scanning techniques showed that the SARS‑CoV‑2 genome contains a large number of fragments that could be recognized by TLR7/TLR8 (Moreno‑Eutimio MA et al. 2020). Upon engagement of ssRNAs in endosomes, TLR7 and TLR8 initiate the MyD88‑dependent pathway, leading to production of type I and type III IFNs and proinflammatory mediators via activation of IRF7 and NF‑κB, respectively (reviewed in Lester SN & Li K 2014). In addition, imidazoquinoline compounds (e.g. imiquimod and R‑848, a small‑molecule immune response modifier that can induce the synthesis of interferon‑alpha) were reported to be ligands of TLR7 and TLR8 (Hemmi H et al. 2002; Jurk M et al. 2002; Diebold SS et al. 2004). Structural analyses have revealed that both TLR7 and TLR8 possess two binding sites (Zhang Z et al. 2016). Binding site 1 is highly conserved between TLR7 and TLR8 and binds nucleosides (guanosine (G) for TLR7 and uridine (U) for TLR8) or base analogs. Binding site 2 of TLR7 and TLR8 is less conserved and binds ssRNA with U(U) and U(G) motifs. TLR7 acts as a dual receptor for G and U‑containing ssRNAs. Binding of ssRNA to the site 2 of TLR7 strongly enhances the interaction of TLR7 and G at the first site leading to subsequent receptor dimerization. Conversely, chemical ligands are sufficiently potent to induce TLR7 dimerization by binding to the first site alone (Zhang Z et al. 2016, 2018). Further, upon ligand stimulation, the TLR8 dimer was reorganized such that the two C termini were brought into proximity (Tanji H et al. 2013). The loop between leucine‑rich repeat 14 (LRR14) and LRR15 was cleaved, but the N‑ and C‑terminal halves remained associated and contributed to ligand recognition and dimerization, which enables the downstream signaling activation of IRF and NF‑κB (Tanji H et al. 2013, 2016). Although TLR7 and TLR8 are phylogenetically and structurally related, TLR7‑ and TLR8‑specific agonists are thought to trigger different cytokine induction profiles. TLR7‑specific agonists generally induce IFN‑regulated cytokines, but TLR8‑specific agonists lead primarily to the production of proinflammatory cytokines (Gorden KB et al. 2005).

羟氯喹（HCQ）结合并拮抗TLR7（Lamphier M等，2014），从而抑制干扰素α产生。HCQ临床使用，治疗全身性狼疮红细胞病和其他自身免疫障碍（Costedoat-Chalumeau N等，2014）。