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. 2021 Jan 23;13(2):170. doi: 10.3390/v13020170

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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RLR signaling pathway. During viral infection, PAMPs in the cytoplasm are recognized by RIG-I and MDA5 leading to their activation. RIG-I and MDA5 interact with IPS-1 adaptor protein located on the mitochondria via its CARD domain. This interaction results in downstream activation of TRAF3, followed by the K63 polyubiquitination (Ub) of TBK1 and IKKi/IKKε, which phosphorylates IRF3 and IRF7, leading to the production of type I IFNs. IPS-1 also activates NF-κB via FADD and RIP1 dependent pathways. FADD and RIP1 form a complex followed by the recruitment of IKKα and IKKβ. This transcription factor complex mediates the translocation of NF-κB (p65/p50) into the nucleus, which initiates the production of inflammatory cytokine. ‘P’ indicates phosphorylation.