Fig. 3

Viruses manipulate the autophagy process. Viruses and viral proteins induce autophagy initiation at different stages of the viral life cycle. In the adsorption stage, MEV combines with CD46-Cyt-1, which is linked to VPS34/Beclin1 complex through the interaction with the GOPC, promoting the formation of autophagosomes. LRV activate TLR3 and TRIF to trigger ATG5-mediated autophagy; ATG5 facilitates the production of TLR9-induced IFN-I in pDCs infected with HSV-1; TLR-7 recognizes RVFV that activates antiviral autophagy through TRAF6 and MyD88. HCV-encoded NS4B triggers the initiation of autophagy by forming a complex with Rab5 and Vps34. Conversely, HSV-1-encoded ICP34.5 binds with Beclin1; v-GPCR encoded by KSHV negatively regulates autophagy. At later stages of autophagy, viruses utilize DMVs as replication or assembly sites. MHV NSP6 induces autophagy to produce DMVs. These DMVs possess double-membrane-spanning molecular pores, which allows RNAs to be exported to the cytosol. CVB3 exploits autophagy to support its replication in DMVs. Virus blocks the fusion of autophagosomes and lysosomes mainly by targeting the SNARE protein, Rab GTPase family and Tethering factors, or disrupting lysosomal function. CVB3 protease 3C, HPIV3 P protein and EVD viral protease target SNAP29 to inhibit autophagy flux. In addition, CVB3 proteinase 3C targets TFEB for proteolytic processing to disrupt lysosomal function. HCV negatively regulates and positively regulates the maturation of autophagosomes by inducing Rubicon or UVRAG, respectively. KSHV and EBV downregulate RAB7 to block autophagy. SARS-COV-2 ORF3a protein sequestrates and interacts with the HOPS component, and ORF7a reduces the fusion with lysosomes. IAV M2 interacting with Beclin1 may prevent the fusion of autophagosomes and lysosomes. Finally, the virus exploits secretory autophagy to promote viral maturation, egress and cell–cell spreading. DENV takes advantage of autophagy-associated vesicles to promote virus transmission. PV is captured by PS lipid-enriched autophagosome-like vesicles, then vesicles are released from cells. EBV or HCMV recruits autophagy-related protein-coupled membranes to its envelope