{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:14:50Z","timestamp":1788394490267,"version":"build-2803163510"},"reference-count":57,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,17]],"date-time":"2024-11-17T00:00:00Z","timestamp":1731801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation Joint Fund project","award":["U22A20527"],"award-info":[{"award-number":["U22A20527"]}]},{"name":"National Natural Science Foundation Joint Fund project","award":["LH2021C041"],"award-info":[{"award-number":["LH2021C041"]}]},{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["U22A20527"],"award-info":[{"award-number":["U22A20527"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["LH2021C041"],"award-info":[{"award-number":["LH2021C041"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Autophagy is an important cellular response against intracellular pathogens. However, some viruses have evolved mechanisms to hijack this defensive process to provide favorable conditions for virus replication in host cells. The porcine epidemic diarrhea virus (PEDV) has been shown to alter autophagy pathways; however, it is still unknown through which receptors PEDV induces autophagy in IPEC-J2 cells, whether autophagy facilitates PEDV replication, and which functional domains of PEDV proteins are primarily responsible for inducing autophagy. Here, we found that PEDV infection induces autophagy in host cells via distinct and uncoupled molecular pathways. RNA-seq technology was used to analyze the expression patterns of intracellular genes in PEDV-infected IPEC-J2 cells using transcriptomics. The results demonstrate that PEDV triggers autophagy via the cellular pathogen receptor TLR4 and the AKT-mTOR pathway. As evidenced by autophagosome detection, PEDV infection increases autophagosomes and light chain 3 (LC3)-II as well as downregulated AKT-mTOR phosphorylation. Our study revealed that the binding of the viral protein NSP61-2C (56-151aa) to TLR4 triggers autophagy and inactivates the AKT-mTOR pathway, both of which are critical for facilitating PEDV infection. Through screening and analysis, TLR4 was found to be a key gene involved in PEDV-induced autophagy. The screening of the key functional domains of NSP6 (56-151aa) for their ability to induce autophagy in IPEC-J2 cells provided a basis for the in-depth analysis of the pathogenic mechanism of PEDV infection-induced autophagy and promotion of self-replication and also provided an important target for the study of PEDV antiviral drugs. In conclusion, we elucidated that the PEDV infection of IPEC-J2 cells could induce autophagy and found that PEDV could use autophagy to promote its own replication.<\/jats:p>","DOI":"10.3390\/v16111787","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T05:36:45Z","timestamp":1731908205000},"page":"1787","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["IPEC-J2 Autophagy Induced by TLR4 and NSP6 Interactions Facilitate Porcine Epidemic Diarrhea Virus Replication"],"prefix":"10.3390","volume":"16","author":[{"given":"Haiyuan","family":"Zhao","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianzhong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry, Heilongjiang Academy of Agricultural Sciences, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinyuan","family":"Chang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Chongqing Academy of Animal Science, Chongqing 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilan","family":"Shao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxuan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Cui","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Tang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijing","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5724-3025","authenticated-orcid":false,"given":"Xiaona","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China"},{"name":"Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1136\/vr.100.12.243","article-title":"An apparently new syndrome of porcine epidemic diarrhoea","volume":"100","author":"Wood","year":"1977","journal-title":"Vet. Rec."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s11262-012-0713-1","article-title":"Porcine epidemic diarrhoea virus: A comprehensive review of molecular epidemiology, diagnosis, and vaccines","volume":"44","author":"Song","year":"2012","journal-title":"Virus Genes"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Jantraphakorn, Y., Viriyakitkosol, R., Jongkaewwattana, A., and Kaewborisuth, C. (2021). Interaction Between PEDV and Its Hosts: A Closer Look at the ORF3 Accessory Protein. Front. Vet. Sci., 8.","DOI":"10.3389\/fvets.2021.744276"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.3201\/eid2010.140491","article-title":"Distinct characteristics and complex evolution of PEDV strains, North America, May 2013\u2013February 2014","volume":"20","author":"Vlasova","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.vetmic.2019.03.009","article-title":"Assessment of the safety and efficacy of an attenuated live vaccine based on highly virulent genotype 2b porcine epidemic diarrhea virus in nursing piglets","volume":"231","author":"Jang","year":"2019","journal-title":"Vet. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1016\/j.vaccine.2009.01.130","article-title":"Escherichia coli expressing single-chain Fv on the cell surface as a potential prophylactic of porcine epidemic diarrhea virus","volume":"27","author":"Pyo","year":"2009","journal-title":"Vaccine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.virusres.2012.10.018","article-title":"Ribavirin efficiently suppresses porcine nidovirus replication","volume":"171","author":"Kim","year":"2013","journal-title":"Virus Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.4161\/auto.7.11.16642","article-title":"Coronavirus nsp6 proteins generate autophagosomes from the endoplasmic reticulum via an omegasome intermediate","volume":"7","author":"Cottam","year":"2011","journal-title":"Autophagy"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"496","DOI":"10.4161\/auto.23465","article-title":"Visualizing the autophagy pathway in avian cells and its application to studying infectious bronchitis virus","volume":"9","author":"Maier","year":"2013","journal-title":"Autophagy"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Guo, X., Zhang, M., Zhang, X., Tan, X., Guo, H., Zeng, W., Yan, G., Memon, A.M., Li, Z., and Zhu, Y. (2017). Porcine Epidemic Diarrhea Virus Induces Autophagy to Benefit Its Replication. Viruses, 9.","DOI":"10.3390\/v9030053"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.antiviral.2017.08.010","article-title":"Rapamycin-induced autophagy restricts porcine epidemic diarrhea virus infectivity in porcine intestinal epithelial cells","volume":"146","author":"Ko","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lin, H., Li, B., Liu, M., Zhou, H., He, K., and Fan, H. (2020). Nonstructural protein 6 of porcine epidemic diarrhea virus induces autophagy to promote viral replication via the PI3K\/Akt\/mTOR axis. Vet. Microbiol., 244.","DOI":"10.1016\/j.vetmic.2020.108684"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"662","DOI":"10.3201\/eid2004.131685","article-title":"Pathology of US porcine epidemic diarrhea virus strain PC21A in gnotobiotic pigs","volume":"20","author":"Jung","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"198045","DOI":"10.1016\/j.virusres.2020.198045","article-title":"Porcine epidemic diarrhea virus (PEDV): An update on etiology, transmission, pathogenesis, and prevention and control","volume":"286","author":"Jung","year":"2020","journal-title":"Virus Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhang, S., Cao, Y., and Yang, Q. (2020). Transferrin receptor 1 levels at the cell surface influence the susceptibility of newborn piglets to PEDV infection. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008682"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.rvsc.2018.06.009","article-title":"Immunohistochemical detection of the vomiting-inducing monoamine neurotransmitter serotonin and enterochromaffin cells in the intestines of conventional or gnotobiotic (Gn) pigs infected with porcine epidemic diarrhea virus (PEDV) and serum cytokine responses of Gn pigs to acute PEDV infection","volume":"119","author":"Jung","year":"2018","journal-title":"Res. Vet. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s00705-017-3652-2","article-title":"Porcine teschovirus 2 induces an incomplete autophagic response in PK-15 cells","volume":"163","author":"Gu","year":"2018","journal-title":"Arch. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1080\/15548627.2019.1643184","article-title":"Autophagy induction by the pathogen receptor NECTIN4 and sustained autophagy contribute to peste des petits ruminants virus infectivity","volume":"16","author":"Yang","year":"2020","journal-title":"Autophagy"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.chom.2009.09.006","article-title":"Autophagy induction by the pathogen receptor CD46","volume":"6","author":"Joubert","year":"2009","journal-title":"Cell Host Microbe"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41422-020-0362-1","article-title":"A novel selective autophagy receptor, CCDC50, delivers K63 polyubiquitination-activated RIG-I\/MDA5 for degradation during viral infection","volume":"31","author":"Hou","year":"2021","journal-title":"Cell Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e00831-20","DOI":"10.1128\/JVI.00831-20","article-title":"Comparison of Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Binding to ACE2 Receptors from Human, Pets, Farm Animals, and Putative Intermediate Hosts","volume":"94","author":"Zhai","year":"2020","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e37","DOI":"10.4110\/in.2021.21.e37","article-title":"Hepatitis B virus X Protein Promotes Liver Cancer Progression through Autophagy Induction in Response to TLR4 Stimulation","volume":"21","author":"Son","year":"2021","journal-title":"Immune Netw."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Leit\u00e3o, E., Ger, K.A., and Panosso, R. (2018). Selective Grazing by a Tropical Copepod (Notodiaptomus iheringi) Facilitates Microcystis Dominance. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.00301"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhang, K., Huang, Q., Deng, S., Yang, Y., Li, J., and Wang, S. (2021). Mechanisms of TLR4-Mediated Autophagy and Nitroxidative Stress. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.766590"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nature09782","article-title":"Autophagy in immunity and inflammation","volume":"469","author":"Levine","year":"2011","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cell.2018.09.048","article-title":"Biological Functions of Autophagy Genes: A Disease Perspective","volume":"176","author":"Levine","year":"2019","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/nri3532","article-title":"Autophagy in infection, inflammation and immunity","volume":"13","author":"Deretic","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/cdd.2008.130","article-title":"Eating the enemy within: Autophagy in infectious diseases","volume":"16","author":"Orvedahl","year":"2009","journal-title":"Cell Death Differ."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.chom.2010.10.006","article-title":"Dengue virus-induced autophagy regulates lipid metabolism","volume":"8","author":"Heaton","year":"2010","journal-title":"Cell Host Microbe"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1080\/15548627.2020.1817280","article-title":"Coronavirus interactions with the cellular autophagy machinery","volume":"16","author":"Miller","year":"2020","journal-title":"Autophagy"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1146\/annurev-genet-102808-114910","article-title":"Regulation mechanisms and signaling pathways of autophagy","volume":"43","author":"He","year":"2009","journal-title":"Annu. Rev. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1080\/15548627.2015.1017184","article-title":"Binding of the pathogen receptor HSP90AA1 to avibirnavirus VP2 induces autophagy by inactivating the AKT-MTOR pathway","volume":"11","author":"Hu","year":"2015","journal-title":"Autophagy"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"182","DOI":"10.3892\/ijmm.2017.3008","article-title":"The PI3K\/Akt\/mTOR pathway is involved in CVB3-induced autophagy of HeLa cells","volume":"40","author":"Chang","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1080\/15548627.2017.1405187","article-title":"Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1-ATF4 pathway and induces autophagy via HSPB1","volume":"14","author":"Sun","year":"2018","journal-title":"Autophagy"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.jviromet.2005.05.005","article-title":"Rapid human metapneumovirus microneutralization assay based on green fluorescent protein expression","volume":"128","author":"Biacchesi","year":"2005","journal-title":"J. Virol. Methods"},{"key":"ref_36","first-page":"84","article-title":"Preparation and Partial Characterization of Monoclonal Antibody against N Protein of Porcine Epidemic Diarrhea Virus","volume":"39","author":"Pei","year":"2008","journal-title":"J. Northeast Agric. Univ."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ncb2152","article-title":"AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1","volume":"13","author":"Kim","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1080\/15548627.2018.1474314","article-title":"Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion","volume":"14","author":"Mauthe","year":"2018","journal-title":"Autophagy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"155581","DOI":"10.1016\/j.cyto.2021.155581","article-title":"Lactobacillus johnsonii activates porcine monocyte derived dendritic cells maturation to modulate Th cellular immune response","volume":"144","author":"Zheng","year":"2021","journal-title":"Cytokine"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ma, S., Qiao, X., Xu, Y., Wang, L., Zhou, H., Jiang, Y., Cui, W., Huang, X., Wang, X., and Tang, L. (2019). Screening and Identification of a Chicken Dendritic Cell Binding Peptide by Using a Phage Display Library. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01853"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Yang, B., Qi, X., Guo, H., Jia, P., Chen, S., Chen, Z., Wang, T., Wang, J., and Xue, Q. (2018). Peste des Petits Ruminants Virus Enters Caprine Endometrial Epithelial Cells via the Caveolae-Mediated Endocytosis Pathway. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.00210"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1080\/21505594.2018.1496776","article-title":"Autophagy enhances the replication of Peste des petits ruminants virus and inhibits caspase-dependent apoptosis in vitro","volume":"9","author":"Yang","year":"2018","journal-title":"Virulence"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2015.1100356","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)","volume":"12","author":"Klionsky","year":"2016","journal-title":"Autophagy"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cell.2007.12.018","article-title":"Autophagy in the pathogenesis of disease","volume":"132","author":"Levine","year":"2008","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/ncb0910-823","article-title":"Autophagy in mammalian development and differentiation","volume":"12","author":"Mizushima","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41579-018-0003-6","article-title":"Autophagy during viral infection\u2014A double-edged sword","volume":"16","author":"Choi","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_47","first-page":"159","article-title":"Eating oneself and uninvited guests: Autophagy-related pathways in cellular defense","volume":"120","author":"Levine","year":"2005","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Liang, S., Wu, Y.S., Li, D.Y., Tang, J.X., and Liu, H.F. (2021). Autophagy in Viral Infection and Pathogenesis. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.766142"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.3390\/v3081332","article-title":"Dengue virus and autophagy","volume":"3","author":"Heaton","year":"2011","journal-title":"Viruses"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Schiffer, L., Barnard, L., Baranowski, E.S., Gilligan, L.C., Taylor, A.E., Arlt, W., Shackleton, C.H.L., and Storbeck, K.H. (2019). Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: A comprehensive review. J. Steroid Biochem. Mol. Biol., 194.","DOI":"10.1016\/j.jsbmb.2019.105439"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Kawasaki, T., and Kawai, T. (2014). Toll-like receptor signaling pathways. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00461"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s13238-017-0409-3","article-title":"mTORC1 signaling in hepatic lipid metabolism","volume":"9","author":"Han","year":"2018","journal-title":"Protein Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/j.1365-2443.2010.01482.x","article-title":"Activating mutations of TOR (target of rapamycin)","volume":"16","author":"Hardt","year":"2011","journal-title":"Genes Cells Devoted Mol. Cell. Mech."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"101250","DOI":"10.1016\/j.tranon.2021.101250","article-title":"USP8 regulates liver cancer progression via the inhibition of TRAF6-mediated signal for NF-\u03baB activation and autophagy induction by TLR4","volume":"15","author":"Kim","year":"2022","journal-title":"Transl. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/bcpt.13497","article-title":"Baicalin inhibits Salmonella typhimurium-induced inflammation and mediates autophagy through TLR4\/MAPK\/NF-\u03baB signalling pathway","volume":"128","author":"Zhang","year":"2021","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.4161\/auto.29309","article-title":"Coronavirus NSP6 restricts autophagosome expansion","volume":"10","author":"Cottam","year":"2014","journal-title":"Autophagy"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e24","DOI":"10.1016\/j.jinf.2020.03.058","article-title":"Evolutionary analysis of SARS-CoV-2: How mutation of Non-Structural Protein 6 (NSP6) could affect viral autophagy","volume":"81","author":"Benvenuto","year":"2020","journal-title":"J. Infect."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/11\/1787\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:34:03Z","timestamp":1760114043000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/11\/1787"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,17]]},"references-count":57,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["v16111787"],"URL":"https:\/\/doi.org\/10.3390\/v16111787","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,17]]}}}