@article{e3494806501d4fd6b8f7451074d90918,
title = "Dengue nonstructural protein 1 maintains autophagy through retarding caspase-mediated cleavage of beclin-1",
abstract = "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.",
keywords = "Apoptosis, Autophagy, Beclin-1, Caspase, Dengue virus, NS1",
author = "Lu, {Zi Yi} and Cheng, {Miao Huei} and Yu, {Chia Yi} and Lin, {Yee Shin} and Yeh, {Trai Ming} and Chen, {Chia Ling} and Chen, {Chien Chin} and Wan, {Shu Wen} and Chang, {Chih Peng}",
note = "Funding Information: Funding: This research was funded by grant number MOST 104-2320-B-006-038-MY3, MOST 108-2320-B-214-007 and MOST 109-2320-B-214-004 from The Ministry of Science and Technology as well as NHRI-109A1-MRCO-02202013 from The National Health Research Institutes. Funding Information: This research was funded by grant number MOST 104-2320-B-006-038-MY3, MOST 108-2320-B-214-007 and MOST 109-2320-B-214-004 from The Ministry of Science and Technology as well as NHRI-109A1-MRCO-02202013 from The National Health Research Institutes. We thank Tamotsu Yoshimori (Department of Genetics, Graduate School of Medicine, Osaka University) for kindly providing Flag-Beclin-1 plasmids. We thank Shan-Tair Wang (Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan) for the help of data consulting. We also thank the technical services provided by the ?Bioimaging Core Facility of the National Core Facility for Biopharmaceuticals, Ministry of Science and Technology, Taiwan?. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = dec,
day = "2",
doi = "10.3390/ijms21249702",
language = "English",
volume = "21",
pages = "1--19",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI AG",
number = "24",
}