{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T09:23:38Z","timestamp":1778059418416,"version":"3.51.4"},"reference-count":42,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T00:00:00Z","timestamp":1665446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"French Armed Forces Health Service","award":["DEQ20170336729"],"award-info":[{"award-number":["DEQ20170336729"]}]},{"name":"Direction G\u00e9n\u00e9rale pour l\u2019Armement (DGA)","award":["DEQ20170336729"],"award-info":[{"award-number":["DEQ20170336729"]}]},{"name":"Fondation pour la Recherche M\u00e9dicale","award":["DEQ20170336729"],"award-info":[{"award-number":["DEQ20170336729"]}]},{"name":"Institut Universitaire de France (IUF)","award":["DEQ20170336729"],"award-info":[{"award-number":["DEQ20170336729"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Dugbe orthonairovirus (DUGV) is a tick-borne arbovirus within the order Bunyavirales. Although displaying mild pathogenic potential, DUGV is genetically related to the Crimean\u2013Congo hemorrhagic fever virus (CCHFV), another orthonairovirus that causes severe liver dysfunction and hemorrhagic fever with a high mortality rate in humans. As we previously observed that CCHFV infection could massively recruit and lipidate MAP1LC3 (LC3), a core factor involved in the autophagic degradation of cytosolic components, we asked whether DUGV infection also substantially impacts the autophagy machinery in epithelial cells. We observed that DUGV infection does impose LC3 lipidation in cultured hepatocytes. DUGV infection also caused an upregulation of the MAP1LC3 and SQSTM1\/p62 transcript levels, which were, however, more moderate than those seen during CCHFV infection. In contrast, unlike during CCHFV infection, the modulation of core autophagy factors could influence both LC3 lipidation and viral particle production: the silencing of ATG5 and\/or ATG7 diminished the induction of LC3 lipidation and slightly upregulated the level of infectious DUGV particle production. Overall, the results are compatible with the notion that in epithelial cells infected with DUGV in vitro, the autophagy machinery may be recruited to exert a certain level of restriction on viral replication. Thus, the relationship between DUGV infection and autophagy in epithelial cells appears to present both similarities and distinctions with that seen during CCHFV infection.<\/jats:p>","DOI":"10.3390\/v14102230","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T02:10:27Z","timestamp":1665540627000},"page":"2230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Relationship between DUGBE Virus Infection and Autophagy in Epithelial Cells"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7132-6329","authenticated-orcid":false,"given":"Marie","family":"Moroso","sequence":"first","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France"},{"name":"Emerging Pathogens Laboratory, Fondation M\u00e9rieux, F-69002 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aurore","family":"Rozi\u00e8res","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1059-4645","authenticated-orcid":false,"given":"Pauline","family":"Verlhac","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1023-0796","authenticated-orcid":false,"given":"Florence","family":"Komurian-Pradel","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France"},{"name":"Emerging Pathogens Laboratory, Fondation M\u00e9rieux, F-69002 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"Ferraris","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France"},{"name":"Emerging Pathogens Laboratory, Fondation M\u00e9rieux, F-69002 Lyon, France"},{"name":"Biomedical Research Institute of the French Army (IRBA), F-91220 Bretigny-sur-Orge, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe N.","family":"Peyrefitte","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France"},{"name":"Emerging Pathogens Laboratory, Fondation M\u00e9rieux, F-69002 Lyon, France"},{"name":"Biomedical Research Institute of the French Army (IRBA), F-91220 Bretigny-sur-Orge, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6369-5837","authenticated-orcid":false,"given":"Glaucia","family":"Paranhos-Baccal\u00e0","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France"},{"name":"Emerging Pathogens Laboratory, Fondation M\u00e9rieux, F-69002 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe","family":"Viret","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias","family":"Faure","sequence":"additional","affiliation":[{"name":"CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm U1111, Universit\u00e9 Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France"},{"name":"Equipe Labellis\u00e9e par la Fondation pour la Recherche M\u00e9dicale, 54 Rue de Varenne, F-75007 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/ncb0910-814","article-title":"Eaten Alive: A History of Macroautophagy","volume":"12","author":"Yang","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1146\/annurev-cellbio-092910-154005","article-title":"The Role of Atg Proteins in Autophagosome Formation","volume":"27","author":"Mizushima","year":"2011","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/ncb2979","article-title":"Cargo Recognition and Trafficking in Selective Autophagy","volume":"16","author":"Stolz","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.molcel.2019.09.005","article-title":"A Diversity of Selective Autophagy Receptors Determines the Specificity of the Autophagy Pathway","volume":"76","author":"Kirkin","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"24131","DOI":"10.1074\/jbc.M702824200","article-title":"P62\/SQSTM1 Binds Directly to Atg8\/LC3 to Facilitate Degradation of Ubiquitinated Protein Aggregates by Autophagy","volume":"282","author":"Pankiv","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.cell.2007.10.035","article-title":"Homeostatic Levels of P62 Control Cytoplasmic Inclusion Body Formation in Autophagy-Deficient Mice","volume":"131","author":"Komatsu","year":"2007","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1146\/annurev-biochem-060815-014556","article-title":"Mammalian Autophagy: How Does It Work?","volume":"85","author":"Bento","year":"2016","journal-title":"Annu. Rev. Biochem."},{"key":"ref_8","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_9","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nrmicro3160","article-title":"Bacteria\u2013Autophagy Interplay: A Battle for Survival","volume":"12","author":"Huang","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/bs.aivir.2016.02.002","article-title":"Autophagy and Mammalian Viruses","volume":"Volume 95","author":"Paul","year":"2016","journal-title":"Advances in Virus Research"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.tim.2021.02.006","article-title":"Selective Autophagy Receptors in Antiviral Defense","volume":"29","author":"Viret","year":"2021","journal-title":"Trends Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1007\/s00705-019-04253-6","article-title":"Taxonomy of the Order Bunyavirales: Update 2019","volume":"164","author":"Abudurexiti","year":"2019","journal-title":"Arch. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.antiviral.2017.05.010","article-title":"The Role of Ticks in the Maintenance and Transmission of Crimean-Congo Hemorrhagic Fever Virus: A Review of Published Field and Laboratory Studies","volume":"144","author":"Gargili","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S1473-3099(06)70435-2","article-title":"Crimean-Congo Haemorrhagic Fever","volume":"6","year":"2006","journal-title":"Lancet Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.antiviral.2004.08.001","article-title":"Crimean\u2014Congo Hemorrhagic Fever","volume":"64","author":"Whitehouse","year":"2004","journal-title":"Antivir. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.antiviral.2013.07.006","article-title":"Crimean-Congo Hemorrhagic Fever: History, Epidemiology, Pathogenesis, Clinical Syndrome and Genetic Diversity","volume":"100","author":"Bente","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.antiviral.2017.08.014","article-title":"Identification of Broadly Neutralizing Monoclonal Antibodies against Crimean-Congo Hemorrhagic Fever Virus","volume":"146","author":"Zivcec","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1017\/S0950268800052687","article-title":"Investigation of Tick-Borne Viruses as Pathogens of Humans in South Africa and Evidence of Dugbe Virus Infection in a Patient with Prolonged Thrombocytopenia","volume":"116","author":"Burt","year":"1996","journal-title":"Epidemiol. Infect."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"855","DOI":"10.4269\/ajtmh.1981.30.855","article-title":"Arbovirus Infections among Laboratory Personnel in Ibadan, Nigeria","volume":"30","author":"Lee","year":"1981","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1080\/00034983.1975.11686983","article-title":"Arthropod-Borne Viral Infections of Man in Nigeria, 1964\u20131970","volume":"69","author":"Moore","year":"1975","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"600","DOI":"10.4269\/ajtmh.1978.27.600","article-title":"Crimean-Congo Hemorrhagic Fever, Thogoto, Dugbe, and Jos Viruses Isolated from Ixodid Ticks in Ethiopia","volume":"27","author":"Casals","year":"1978","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"279","DOI":"10.7589\/0090-3558-10.3.279","article-title":"Isolation of viruses from wild mammals in west africa, 1966\u20131970","volume":"10","author":"Kemp","year":"1974","journal-title":"J. Wildl. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/0021-9975(78)90005-1","article-title":"The Serological Relationships of Nairobi Sheep Disease Virus","volume":"88","author":"Davies","year":"1978","journal-title":"J. Comp. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1159\/000149175","article-title":"The Nairovirus Genus: Serological Relationships","volume":"14","author":"Casals","year":"1980","journal-title":"Intervirology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0168-1702(92)90009-X","article-title":"Expression of the Nucleocapsid Protein of Dugbe Virus and Antigenic Cross-Reactions with Other Nairoviruses","volume":"24","author":"Ward","year":"1992","journal-title":"Virus Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Hartlaub, J., Keller, M., and Groschup, M.H. (2021). Deciphering Antibody Responses to Orthonairoviruses in Ruminants. Microorganisms, 9.","DOI":"10.3390\/microorganisms9071493"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hartlaub, J., Gutjahr, B., Fast, C., Mirazimi, A., Keller, M., and Groschup, M.H. (2021). Diagnosis and Pathogenesis of Nairobi Sheep Disease Orthonairovirus Infections in Sheep and Cattle. Viruses, 13.","DOI":"10.3390\/v13071250"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1006\/viro.2002.1514","article-title":"Nairobi Sheep Disease Virus, an Important Tick-Borne Pathogen of Sheep and Goats in Africa, Is Also Present in Asia","volume":"303","author":"Marczinke","year":"2002","journal-title":"Virology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.virol.2003.09.021","article-title":"The High Genetic Variation of Viruses of the Genus Nairovirus Reflects the Diversity of Their Predominant Tick Hosts","volume":"318","author":"Honig","year":"2004","journal-title":"Virology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1099\/vir.0.015701-0","article-title":"Differential Activation Profiles of Crimean-Congo Hemorrhagic Fever Virus- and Dugbe Virus-Infected Antigen-Presenting Cells","volume":"91","author":"Peyrefitte","year":"2010","journal-title":"J. Gen. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rodrigues, R., Paranhos-Baccal\u00e0, G., Vernet, G., and Peyrefitte, C.N. (2012). Crimean-Congo Hemorrhagic Fever Virus-Infected Hepatocytes Induce ER-Stress and Apoptosis Crosstalk. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029712"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1080\/15548627.2019.1709765","article-title":"Crimean-Congo Hemorrhagic Fever Virus Replication Imposes Hyper-Lipidation of MAP1LC3 in Epithelial Cells","volume":"16","author":"Moroso","year":"2020","journal-title":"Autophagy"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Richetta, C., Gr\u00e9goire, I.P., Verlhac, P., Azocar, O., Baguet, J., Flacher, M., Tangy, F., Rabourdin-Combe, C., and Faure, M. (2013). Sustained Autophagy Contributes to Measles Virus Infectivity. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003599"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.jviromet.2011.06.003","article-title":"Development of a One Step Real Time RT-PCR Assay to Detect and Quantify Dugbe Virus","volume":"176","author":"Rodrigues","year":"2011","journal-title":"J. Virol. Methods"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Arnoldi, F., De Lorenzo, G., Mano, M., Schraner, E.M., Wild, P., Eichwald, C., and Burrone, O.R. (2014). Rotavirus Increases Levels of Lipidated LC3 Supporting Accumulation of Infectious Progeny Virus without Inducing Autophagosome Formation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095197"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"323","DOI":"10.4161\/auto.4012","article-title":"LC3, an Autophagosome Marker, Can Be Incorporated into Protein Aggregates Independent of Autophagy: Caution in the Interpretation of LC3 Localization","volume":"3","author":"Kuma","year":"2007","journal-title":"Autophagy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"648077","DOI":"10.3389\/fcimb.2021.648077","article-title":"Differential Cell Line Susceptibility to Crimean-Congo Hemorrhagic Fever Virus","volume":"11","author":"Dai","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"16739","DOI":"10.1074\/jbc.M414139200","article-title":"Distinct Poly(I-C) and Virus-Activated Signaling Pathways Leading to Interferon-\u03b2 Production in Hepatocytes","volume":"280","author":"Li","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kozak, R.A., Fraser, R.S., Biondi, M.J., Majer, A., Medina, S.J., Griffin, B.D., Kobasa, D., Stapleton, P.J., Urfano, C., and Babuadze, G. (2020). Dual RNA-Seq Characterization of Host and Pathogen Gene Expression in Liver Cells Infected with Crimean-Congo Hemorrhagic Fever Virus. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008105"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.4161\/auto.7.12.17793","article-title":"Vaccinia Virus Leads to ATG12\u2013ATG3 Conjugation and Deficiency in Autophagosome Formation","volume":"7","author":"Moloughney","year":"2011","journal-title":"Autophagy"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.chom.2014.04.004","article-title":"Phosphoprotein of Human Parainfluenza Virus Type 3 Blocks Autophagosome-Lysosome Fusion to Increase Virus Production","volume":"15","author":"Ding","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e76071","DOI":"10.7554\/eLife.76071","article-title":"Multi-Omics Insights into Host-Viral Response and Pathogenesis in Crimean-Congo Hemorrhagic Fever Viruses for Novel Therapeutic Target","volume":"11","author":"Neogi","year":"2022","journal-title":"eLife"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/10\/2230\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:49:41Z","timestamp":1760143781000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/10\/2230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,11]]},"references-count":42,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["v14102230"],"URL":"https:\/\/doi.org\/10.3390\/v14102230","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,11]]}}}