Fig. 4

Autophagy and the innate immune in viral infection. The genetic material of RNA or DNA viruses is recognized by PRRs or cGAS, which facilitate viral induction of antiviral autophagy to improve the IFN production, thereby limiting virus replication. Specifically, VSV and RVFV activate antiviral autophagy and increase the production of type I IFNs through TLR-7 and MYD88 signal transduction; while LRV achieves it through TLR3 and TRIF, which triggers the degradation of NLRP3; HSV activates autophagy and induces interferon production through TLR9. STING-dependent autophagy induced by inflammation limits ZIKV infection. IAV M2 protein increases the formation of MAVS aggregates. It antagonizes autophagy through reducing the formation of ATG5-MAVS and LC3B-MAVS complexes, thereby enhancing the innate immune response. Conversely, HCV inhibits the innate immune response by inducing the autophagic degradation of TRAF6. During the HPV-1 infection, the interaction between cGAS and Beclin1 not only halts the production of IFN by inhibiting the synthesis of cGAMP, but also prevents excessive activation of cGAS to sustain systematic immune balance by enhancing autophagy degradation of viral DNAs. APCs initiate adaptive immunity by presenting protein fragments through MHC. M1 protein of Influenza is targeted by LC3 to autophagosomes, which fuse with MIIC to enhance the antigen presentation of CD4⁺ T cells. LC3 combined with HIV/SIV gag antigen targeted to autophagosomes enhance the HIV-specific CD4⁺ T cell response. HIV-1 envelope and ICP34.5 of HSV1 inhibit autophagy in DCs, escaping MHC-restricted presentation of its antigens. ORF8 of SARS-CoV-2 directly interacts with MHC Ι and mediates its down-regulation through autophagy to evade immune surveillance. HSV-1 infection induces autophagy and increases the presentation of peptides derived from HSV-1 glycoprotein B to CD8⁺ T cells in a manner that requires proteasome function and secretion pathways. Similarly, pUL138 of HCMV is presented by autophagy in a TAP-independent manner that involves MHC I loading in endosomal compartments