Fig. 3

Autophagy in antiviral immune responses

The innate immune system is the first line of defense in multicellular organisms that initiates proinflammatory responses to protect against host tissue damage and microbial invasion such as virus infection. Along with the enhancement of this innate response, autophagy is activated to trap specific pathogens and transport them into autophagosomes for degradation. During viral infection, TLRs of the PRRs family are the primary proteins responsible for initiating innate immune responses and inducing autophagy in mammals. TLR signaling increases the interaction of MyD88 or TRIF with BECN1 and promotes the dissociation of BECN1 from Bcl-2 to promote autophagy. TLR-induced autophagy belongs to selective autophagy (known as xenophagy) that occurs in a ubiquitin-dependent manner. When the virus enters the organism, the viral nucleocapsid is uncoated to be exposed in the cytoplasm by the late endosome or lysosome. TLR signaling pathways are activated by the unique dsRNA, ssRNA, or dsDNA of invading viruses with decapsulated capsid. Interaction between TLRs and MyD88 or TRIF, both of which are responsible for the activation of transcription factors including NF-κB, IRF3/7, and API-1 triggers IFN-I generation and proinflammatory cytokines secretion, which are key immune responses against viruses, and further stimulates factors for innate immune responses. Additionally, autophagy contributes to antigen presentation. In detail, autophagy promotes the upload of the peptides derived from the pathogen into MHC-II molecules for presentation to CD4⁺ T cells, in addition to participating in an alternative pathway of class I presentation, also termed cross-presentation

Abbreviations: BECN1: beclin1; dsRNA: double-stranded RNA; MHC-II: major histocompatibility complex class II; MyD88: myeloid differentiation primary response gene 88; NF-κB: nuclear factor kappa B; PRRs: pattern recognition receptors; ssRNA: single-stranded RNA; TLRs: Toll-like receptors; TRIF: TIR domain-containing adaptor molecule 1