Fig. 4.

Regulation of host and viral circRNAs by host immune response during viral infection. In noninfected cells, NF90/NF110 localized to the nuclear to promote circRNA biogenesis [63]. Upon viral infection, NF90/NF110 is exported to the cytoplasm to suppress viral replication by targeting viral mRNA. OAS‐activated RNase L would degrade cellular dsRNA‐containing circRNAs bound to PKR that eventually lead to the release and activation of PKR. Both exogenous (not m⁶A‐modified) and degraded circRNAs are postulated to activate RIG‐I [58, 64]. Activation of PKR and RIG‐1 ultimately leads to innate immune response to eliminate virus in the host. However, it remains inconclusive if exogenous circRNA is immunogenic [57, 58, 61].