Figure 2.

Innate immune signaling pathways that are known to be activated during viral infection and replication. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human cells through the angiotensin-converting enzyme 2 (ACE2 receptor) and the cellular serine protease TMPRSS2 for viral S protein priming. Following cellular entry, the virus RNA genome may be recognized by pattern recognition receptors (PRR)s, including endosomal Toll-like receptor (TLR)3 and TLR7 recognizing double-stranded and single-stranded RNA, respectively. In the cytosol the virus may be recognized by the retinoic acid inducible receptor (RIG)-I or the melanoma differentiation-associated protein (MDA)5. Following viral recognition by PRRs, this triggers signaling through IFN regulatory factor (IRF)3 and NF-κB to induce IFNs and pro-inflammatory cytokines. Similar responses may be activated by extracellular virus through TLR4.