Dengue Nonstructural Protein 1 Maintains Autophagy through Retarding Caspase-Mediated Cleavage of Beclin-1

doi:10.3390/ijms21249702

Chia Nan University of Pharmacy & Science Institutional Repository > 藥理學院 > 化妝品應用與管理系(所) > 期刊論文 > Item 310902800/34128

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標題:	Dengue Nonstructural Protein 1 Maintains Autophagy through Retarding Caspase-Mediated Cleavage of Beclin-1
作者:	Lu, Zi-Yi Cheng, Miao-Huei Yu, Chia-Yi Lin, Yee-Shin Yeh, Trai-Ming Chen, Chia-Ling Chen, Chien-Chin Wan, Shu-Wen Chang, Chih-Peng
貢獻者:	Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol I Shou Univ, Coll Med, Sch Med Int Students Natl Hlth Res Inst, Natl Inst Infect Dis & Vaccinol Natl Cheng Kung Univ, Ctr Infect Dis & Signaling Res Natl Cheng Kung Univ, Coll Med, Dept Med Lab Sci & Biotechnol Taipei Med Univ, Coll Med, Sch Resp Therapy Taipei Med Univ, Wan Fang Hosp, Pulm Res Ctr Ditmanson Med Fdn Chia Yi Christian Hosp, Dept Pathol Chia Nan Univ Pharm & Sci, Dept Cosmet Sci I Shou Univ, Coll Med, Dept Med Lab Sci Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci
關鍵字:	dengue virus autophagy apoptosis Beclin-1 caspase NS1
日期:	2020
上傳時間:	2022-11-18 11:25:09 (UTC+8)
出版者:	Mdpi
摘要:	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.
關聯:	International Journal of Molecular Sciences, v.21, n.24, pp.19
显示于类别:	[化妝品應用與管理系(所)] 期刊論文

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