{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:01:20Z","timestamp":1791856880727,"version":"4.3.4"},"reference-count":54,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,19]],"date-time":"2020-12-19T00:00:00Z","timestamp":1608336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Ministry of Science and Technology, Taiwan","award":["MOST 104-2320-B-006 -038 -MY3, MOST 108-2320-B-214-007 and MOST 109-2320-B-214-004"],"award-info":[{"award-number":["MOST 104-2320-B-006 -038 -MY3, MOST 108-2320-B-214-007 and MOST 109-2320-B-214-004"]}]},{"name":"The National Health Research Institutes, Taiwan","award":["NHRI-109A1-MRCO-02202013"],"award-info":[{"award-number":["NHRI-109A1-MRCO-02202013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dengue virus (DENV) infection is a significant public health threat in tropical and subtropical regions; however, there is no specific antiviral drug. Accumulated studies have revealed that DENV infection induces several cellular responses, including autophagy and apoptosis. The crosstalk between autophagy and apoptosis is associated with the interactions among components of these two pathways, such as apoptotic caspase-mediated cleavage of autophagy-related proteins. Here, we show that DENV-induced autophagy inhibits early cell apoptosis and hence enhances DENV replication. Later, the apoptotic activities are elevated to suppress autophagy through cleavage of Beclin-1, an essential autophagy-related protein. Inhibition of cleavage of Beclin-1 by a pan-caspase inhibitor, Z-VAD, increases both autophagy and viral replication. Regarding the mechanism, we further found that DENV nonstructural protein 1 (NS1) is able to interact with Beclin-1 during DENV infection. The interaction between Beclin-1 and NS1 attenuates Beclin-1 cleavage and facilitates autophagy to prevent cell apoptosis. Our study suggests a novel mechanism whereby NS1 preserves Beclin-1 for maintaining autophagy to antagonize early cell apoptosis; however, elevated caspases trigger apoptosis by degrading Beclin-1 in the late stage of infection. These findings suggest implications for anti-DENV drug design.<\/jats:p>","DOI":"10.3390\/ijms21249702","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T01:01:08Z","timestamp":1608512468000},"page":"9702","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Dengue Nonstructural Protein 1 Maintains Autophagy through Retarding Caspase-Mediated Cleavage of Beclin-1"],"prefix":"10.3390","volume":"21","author":[{"given":"Zi-Yi","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao-Huei","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung 824, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Yi","family":"Yu","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 350, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee-Shin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trai-Ming","family":"Yeh","sequence":"additional","affiliation":[{"name":"Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Ling","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Pulmonary Research Center, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9599-0884","authenticated-orcid":false,"given":"Chien-Chin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 600, Taiwan"},{"name":"Department of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Wen","family":"Wan","sequence":"additional","affiliation":[{"name":"School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung 824, Taiwan"},{"name":"Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Department of Medical Laboratory Science, College of Medicine, I-Shou University, Kaohsiung 824, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Peng","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"The Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,19]]},"reference":[{"key":"ref_1","first-page":"504","article-title":"The Global Distribution and Burden of Dengue and Japanese Encephalitis Co-Infection in Acute Encephalitis Syndrome","volume":"496","author":"Saxena","year":"2019","journal-title":"Curr. 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