Selective autophagy (SA) | Virus name | Targeted cargos | SA receptors | SA associated factors | Interaction with the autophagy machinery | Effects | Refs. |
---|---|---|---|---|---|---|---|
Virophagy | VSV | – | - | TLR7 | Glycoprotein G of VSV is detected by TLR7, and activates autophagy via the nutrient-sensing phosphoinositide 3-kinase-Akt signalling pathway | Autophagy restricts VSV replication | [146] |
RVFV | – | p62 | TLR-7, TRAF6, MYD88 | Drosophila TLR-7 recognizes RVFV, which activates antiviral autophagy through TRAF6 and MyD88 | Autophagy restricts RVFV replication | [147] | |
Orsay virus | Pathogen proteins | – | Ubiquitin | Orsay virus upregulates and enriches functional domains associated with ubiquitin-mediated proteolysis, including the ubiquitin ligase adapter F-box and MATH domain genes; on this basis, knockdown of an autophagy gene increases the pathogen load | Activation of autophagy reduces the pathogen load of Orsay virus | [148] | |
SINV | SINV capsid protein | P62 | – | p62 interacts with SINV capsid protein; knockdown of p62 blocks the targeting of viral capsid to autophagosomes | Autophagy protects against SINV infection and slows down virus-induced cell death | [149] | |
HBV | viral core proteins | P62 | Galectin-9 | Galectin-9 restricts HBV replication via p62 -mediated selective autophagy of viral core proteins | Autophagy restricts HBV replication | [150] | |
HSV-1 | HSV-1 nucleocapsids and viral particles | – | FANCC | The nucleocapsid of HSV-1 is captured by autophagosomes during its transition through the cytoplasm, which is regulated by FANCC | FANCC mediated virophagy reduces the host’s susceptibility to HSV-1 | [151] | |
IAV | – | – | ATG16L1 | Activation of non‐canonical autophagy causes LAP to control the microbial infection in vivo, inhibiting the fusion of IAV envelope with endosomes and facilitating the presentation of antigens on MHC II molecules | Non-canonical autophagy limits lethal infection by IAV | ||
CCHFV | – | – | LC3 | CCHFV causes a massive lipidation of LC3 in hepatocytes | The genetic alteration of autophagy does not affect CCHFV replication | [155] | |
Mitophagy | IAV | Mitochondria | – | Ripk2 | Ripk2−/− cells (accumulation of damaged mitochondria in cells) infected with IAV exhibit activated NLRP3 and increased levels of IL-18 and IL-1β | NOD-RIPK2 mediated mitophagy protects the host against virally triggered immunopathology | [173] |
IAV | Mitochondria | – | MAVs | M2 protein increases the formation of ROS-dependent MAVS aggregates, while antagonizing the autophagy to reduce the MAVS aggregates degradation | M2 protein inhibits mitophagy and promotes innate immunity | [174] | |
IAV | Mitochondria | PB1-F2 | MAVs, TUMF | PB1-F2 protein acts as an autophagy receptor and mediates the induction of complete mitophagy by simultaneously interacting with LC3B and TUFM, thereby increasing MAVS degradation | PB1-F2 protein promotes mitophagy, and weakens the production of type I IFN | ||
IAV | Mitochondria | NBR1 | RIG-I; MAVs | PB1 preferentially associates with NBR1 that recognizes ubiquitinated MAVS and delivers it to autophagosomes for degradation | PB1 facilitates H7N9 virus infection by inhibiting innate immune signalling | [180] | |
HIV | Mitochondria | P62 | NLRP3 | HIV infection causes mitochondrial accumulation, thereby reducing the negative regulation of NLRP3 | Inhibition of mitophagy up-regulates inflammation | ||
Human herpesvirus 8 (HHV-8) | Mitochondria | NIX | – | HHV-8-encoded viral interferon regulatory factor 1 (vIRF-1) binds to NIX to activate mitophagy | Activation of mitophagy maintains mitochondrial homeostasis and promotes HHV-8 replication | [164] | |
EBV | Mitochondria | NDP52 | PINK1, MAVs-STING; | EBV encoded BHRF1 disturbs mitochondrial dynamics and stimulates mitophagy | Mitophagy inhibits the type I interferon response | [167] | |
HPIV3 | Mitochondria | – | TUFM | The M protein of HPIV3 translocates to mitochondria and interacts with TUFM to induce mitophagy | Mitophagy inhibits the type I interferon response | [168] | |
SARS-CoV-2 | Mitochondria | – | RIG-I-MAVs | The M protein of SARS-COV2 translocates to mitochondria to induce mitophagy | Mitophagy inhibits RIG-MAVS-mediated IFN-β signalling | [170] | |
ER-phagy | DENV/ ZIKV | ER | FAM134B | – | DENV/ ZIKV NS3-mediated cleavage of FAM134B blocks the formation of ER and viral protein-enriched autophagosomes | Flavivirus inhibits ER-phagy to promote its replication | [182] |
DENV/ ZIKV | ER | FAM134B | BPIFB3 | Depletion of BPIFB3 enhances the FAM134B-mediated ER-phagy | ER-phagy facilitates Flavivirus replication | [184] | |
EBOV | ER | FAM134B | – | FAM134B-mediated ER-phagy contributes to the degradation of viral components accumulated in the ER | Replication of EBOV is limited by FAM134B-dependent ER-phagy | [183] | |
WNV/DENV/ ZIKV | ER | RTN3.1A | – | WNV encoded NS4A protein binds RTN3.1A to hijack ER membranes, generates a replication permissive niche to remodel the host membrane and stabilize the viral protein in the ER | Flaviviruses target RTN3.1A to avoid ER-phagy, thereby promoting viral replication | [186] | |
Lipophagy | DENV | Lipid droplets | – | – | Lipophagy is activated and reposited triglycerides are depleted, resulting in an increase in the release of β-oxidized fatty acids in mitochondria, which generates ATP | Lipophagy- generated ATP is required for virus replication and assembly | [191] |
DENV/ ZIKV | Lipid droplets | – | AUP1 | DENV-NS4A exploits the acyltransferase activity of AUP1 to trigger lipophagy and leads AUP1 to relocalize from LDs to autophagosomes upon infection | Flaviviruses exploit the AUP1 to trigger lipophagy and increase progeny virus production | [192] | |
Aggrephagy | MCMV | Aggregates | – | RIPK1, NEMO, TBC1D, VPS26B 5 | MCMV M45 protein requires IPAM to induce aggregation and degradation of RIPK1 and NEMO, then M45 recruits TBC1D5 and VPS26B to facilitate degradation of aggregates | MCMV induced-aggrephagy contributes to immune evasion of the virus and cell viability | [197] |
Ferritinophagy | HCMV | Ferritin | NCOA4 | – | pUL38 protein of HCMV antagonizes USP24 to reduce ferritinophagy | Reduced ferritinophagy increases cell viability and successful virus infection | [204] |
HPIV2 | Ferritin | NCOA4 | FTH1 | V-2 protein of HPIV2 weakens ferritinophagy by interfering with the interaction between FTH1 and NCOA4 | Reduced ferritinophagy allows infected cells to avoid apoptotic cell death, leading to effective viral replication of HPIV2 | [205] |