# Role of autophagy in antiviral innate immunity

**Authors:** Jiufeng Xie, Pengtao Jiao, Dong Wang, Manyu Shi, Cui Yuan, Lijuan Su, Guozhi Zhang, Yuhe Wang, Zhenling Ma, Liqing Li, Wei Liu

PMC · DOI: 10.1186/s11658-026-00871-6 · 2026-02-24

## TL;DR

This paper reviews how autophagy helps the body's innate immune system fight viruses and how some viruses avoid this process.

## Contribution

The paper summarizes key molecules and mechanisms linking autophagy to antiviral innate immunity.

## Key findings

- Autophagy activates innate immunity by triggering interferon production during viral infections.
- Autophagy targets viral components for degradation and supports adaptive immunity via antigen presentation.
- Some viruses inhibit autophagy to evade immune detection and cause disease.

## Abstract

Autophagy exerts an important effect on preserving homeostasis of cellular metabolism through degrading superfluous intracellular components. In addition, it serves as the defense mechanism for eliminating invading pathogens, such as viruses, by the host. The onset of a viral infection triggers autophagy, thereby initiating the innate immunity via the pattern recognition receptor pathways. As a result, interferons and other proinflammatory factors are produced. Furthermore, autophagy specifically targets immune components linked to viral particles for degradation. Through presenting virus-derived antigens to T lymphocytes, this process supports adaptive immunity. Nonetheless, certain viruses evolve mechanisms for inhibiting autophagy, enabling evasion of degradation and immune detection, since autophagy is frequently related to inflammatory diseases, including infections, autoimmune disorders, cancer, metabolic syndromes, neurodegenerative conditions, and cardiovascular and liver diseases. This review aims to summarize the current knowledge regarding the key molecules and specific molecular mechanisms that underlie the pattern recognition receptor signaling where autophagy is implicated during viral infections.

## Linked entities

- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** Pycard (PYD and CARD domain containing) [NCBI Gene 66824] {aka 9130417A21Rik, Asc, CARD5, TMS-1, TNS1, masc}, STING1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 340061] {aka ERIS, MITA, MPYS, NET23, SAVI, STING}, MAP1LC3B (microtubule associated protein 1 light chain 3 beta) [NCBI Gene 81631] {aka ATG8F, LC3B, MAP1A/1BLC3, MAP1LC3B-a}, GABARAPL2 (GABA type A receptor associated protein like 2) [NCBI Gene 11345] {aka ATG8, ATG8C, GATE-16, GATE16, GEF-2, GEF2}, HSPA8 (heat shock protein family A (Hsp70) member 8) [NCBI Gene 3312] {aka HEL-33, HEL-S-72p, HSC54, HSC70, HSC71, HSP71}, NLRX1 (NLR family member X1) [NCBI Gene 79671] {aka CLR11.3, DLNB26, NOD26, NOD5, NOD9}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, ISG15 (ISG15 ubiquitin like modifier) [NCBI Gene 9636] {aka G1P2, IFI15, IMD38, IP17, UCRP, hUCRP}, TLR7 (toll like receptor 7) [NCBI Gene 51284] {aka IMD74, SLEB17, TLR7-like}, ULK1 (unc-51 like autophagy activating kinase 1) [NCBI Gene 8408] {aka ATG1, ATG1A, UNC51, Unc51.1, hATG1}, TLR2 (toll like receptor 2) [NCBI Gene 7097] {aka CD282, TIL4}, IKBKB (inhibitor of nuclear factor kappa B kinase subunit beta) [NCBI Gene 3551] {aka IKK-2, IKK-beta, IKK2, IKKB, IMD15, IMD15A}, Irgm1 (immunity-related GTPase family M member 1) [NCBI Gene 15944] {aka Ifggd3, Ifi1, Iigp3, Iipg3, Irgm}, elap (eye lens aplasia) [NCBI Gene 13708] {aka lap}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, MAVS (mitochondrial antiviral signaling protein) [NCBI Gene 57506] {aka CARDIF, IPS-1, IPS1, VISA}, Casp1 (caspase 1) [NCBI Gene 12362] {aka ICE, Il1bc}, NFKB2 (nuclear factor kappa B subunit 2) [NCBI Gene 4791] {aka CVID10, H2TF1, LYT-10, LYT10, NF-kB2, p100}, ATG5 (autophagy related 5) [NCBI Gene 9474] {aka APG5, APG5-LIKE, APG5L, ASP, SCAR25, hAPG5}, TBK1 (TANK binding kinase 1) [NCBI Gene 29110] {aka AIARV, FTDALS4, IIAE8, NAK, T2K}, TOMM40 (translocase of outer mitochondrial membrane 40) [NCBI Gene 10452] {aka C19orf1, D19S1177E, PER-EC1, PEREC1, TOM40}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, IFIH1 (interferon induced with helicase C domain 1) [NCBI Gene 64135] {aka AGS7, Hlcd, IDDM19, IMD95, MDA-5, MDA5}, OTUD7B (OTU deubiquitinase 7B) [NCBI Gene 56957] {aka CEZANNE, ZA20D1}, IRF3 (interferon regulatory factor 3) [NCBI Gene 3661] {aka IIAE7}, Trim16 (tripartite motif-containing 16) [NCBI Gene 94092] {aka 9130006M08Rik, EBBP}, TUFM (Tu translation elongation factor, mitochondrial) [NCBI Gene 7284] {aka COXPD4, EF-TuMT, EFTU, P43}, PRKN (parkin RBR E3 ubiquitin protein ligase) [NCBI Gene 5071] {aka AR-JP, LPRS2, PARK2, PDJ}, TRAF6 (TNF receptor associated factor 6) [NCBI Gene 7189] {aka MGC:3310, RNF85}, PLEKHM1 (pleckstrin homology and RUN domain containing M1) [NCBI Gene 9842] {aka AP162, B2, OPTA3, OPTB6}, TRIM21 (tripartite motif containing 21) [NCBI Gene 6737] {aka RNF81, RO52, Ro/SSA, SSA, SSA1, TRIM21/Ro52}, RB1CC1 (RB1 inducible coiled-coil 1) [NCBI Gene 9821] {aka ATG17, CC1, FIP200, PPP1R131}, CASP1 (caspase 1) [NCBI Gene 834] {aka ICE, IL1BC, P45}, CALCOCO2 (calcium binding and coiled-coil domain 2) [NCBI Gene 10241] {aka NDP52}, PLP2 (proteolipid protein 2) [NCBI Gene 5355] {aka A4, A4LSB}, IRF1 (interferon regulatory factor 1) [NCBI Gene 3659] {aka IMD117, IRF-1, MAR}, IKBKE (inhibitor of nuclear factor kappa B kinase subunit epsilon) [NCBI Gene 9641] {aka IKK-E, IKK-i, IKKE, IKKI}, ATG3 (autophagy related 3) [NCBI Gene 64422] {aka APG3, APG3-LIKE, APG3L, PC3-96, hApg3}, TLR8 (toll like receptor 8) [NCBI Gene 51311] {aka CD288, IMD98, TLR-8, hTLR8}, TICAM1 (TIR domain containing adaptor molecule 1) [NCBI Gene 148022] {aka IIAE6, MyD88-3, PRVTIRB, TICAM-1, TRIF}, PINK1 (PTEN induced kinase 1) [NCBI Gene 65018] {aka BRPK, PARK6}, SQSTM1 (sequestosome 1) [NCBI Gene 8878] {aka A170, DMRV, EBIAP, FTDALS3, NADGP, OSIL}, UVRAG (UV radiation resistance associated) [NCBI Gene 7405] {aka DHTX, VPS38, p63}, PIK3C3 (phosphatidylinositol 3-kinase catalytic subunit type 3) [NCBI Gene 5289] {aka VPS34, Vps34, hVps34}, TAX1BP1 (Tax1 binding protein 1) [NCBI Gene 8887] {aka CALCOCO3, T6BP, TXBP151}, Atg16l1 (autophagy related 16 like 1) [NCBI Gene 77040] {aka 1500009K01Rik, Apg16l, Atg16l, WDR30}, PRKAA2 (protein kinase AMP-activated catalytic subunit alpha 2) [NCBI Gene 5563] {aka AMPK, AMPK2, AMPKa2, PRKAA}, VAMP8 (vesicle associated membrane protein 8) [NCBI Gene 8673] {aka EDB, VAMP-8}, MYD88 (MYD88 innate immune signal transduction adaptor) [NCBI Gene 4615] {aka IMD68, MYD88D, WM1}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, ATG101 (autophagy related 101) [NCBI Gene 60673] {aka C12orf44}, Tbk1 (TANK-binding kinase 1) [NCBI Gene 56480] {aka 1200008B05Rik}, TLR5 (toll like receptor 5) [NCBI Gene 7100] {aka MELIOS, SLE1, SLEB1, TIL3}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, Trim11 (tripartite motif-containing 11) [NCBI Gene 94091], TNF receptor-associated factor 6 [NCBI Gene 222344], SARM1 (sterile alpha and TIR motif containing 1) [NCBI Gene 23098] {aka HsTIR, MyD88-5, SAMD2, SARM, hSARM1}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}
- **Diseases:** death (MESH:D003643), infection (MESH:D007239), septic shock (MESH:D012772), NLRs (MESH:D064128), neurodegenerative conditions (MESH:D019636), uveitis (MESH:D014605), neuroinflammation (MESH:D000090862), sepsis (MESH:D018805), Crohn's disease (MESH:D003424), cancer (MESH:D009369), viral infection (MESH:D014777), HSV-1 infection (MESH:D006561), autoimmune conditions (MESH:D001327), melanoma (MESH:D008545), COVID-19 (MESH:D000086382), head and neck squamous cell carcinoma (MESH:D000077195), inflammation (MESH:D007249), cardiovascular and liver diseases (MESH:D008107), Infectious Diseases (MESH:D003141), metabolic syndromes (MESH:D024821), IAV infection (MESH:D007251)
- **Chemicals:** poly(dA:dT) (MESH:D011067), LC3 (-), trehalose (MESH:D014199), glycogen (MESH:D006003), GTP (MESH:D006160), CpG dinucleotides (MESH:C015772), ROS (MESH:D017382), proton (MESH:D011522), PtdIns(3)P (MESH:C055525), Poly(I:C) (MESH:D011070), nucleotide (MESH:D009711), glucose (MESH:D005947), cyclic di-GMP (MESH:C062025), PE (MESH:C483858), ATP (MESH:D000255), LPS (MESH:D008070)
- **Species:** Classical swine fever virus (no rank) [taxon 11096], Human immunodeficiency virus 1 (no rank) [taxon 11676], Sindbis virus (no rank) [taxon 11034], Vesicular stomatitis virus (species) [taxon 11276], rhinovirus A16 (no rank) [taxon 31708], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Coxsackievirus B3 (no rank) [taxon 12072], Coronaviridae (family) [taxon 11118], Coxsackievirus A16 (no rank) [taxon 31704], Human papillomavirus (species) [taxon 10566], Mus musculus (house mouse, species) [taxon 10090], Japanese encephalitis virus (no rank) [taxon 11072], Dengue virus (no rank) [taxon 12637], Severe acute respiratory syndrome-related coronavirus (no rank) [taxon 694009], Human respirovirus 3 (no rank) [taxon 11216], simian virus 5 [taxon 1979162], Middle East respiratory syndrome-related coronavirus (no rank) [taxon 1335626], Homo sapiens (human, species) [taxon 9606], Human alphaherpesvirus 1 (Herpes simplex virus type 1, no rank) [taxon 10298], Orthopoxvirus vaccinia (species) [taxon 10245], Gammacoronavirus (genus) [taxon 694013], human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376], Enterovirus A71 (no rank) [taxon 39054], Murine norovirus (no rank) [taxon 357231], Respiratory syncytial virus (no rank) [taxon 12814], hepatitis C virus [taxon 11103], Influenza A virus (no rank) [taxon 11320], Human betaherpesvirus 5 (no rank) [taxon 10359], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932]
- **Cell lines:** HEK293T — Homo sapiens (Human), Transformed cell line (CVCL_0063)

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13037318/full.md

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Source: https://tomesphere.com/paper/PMC13037318