國家衛生研究院 NHRI:Item 3990099045/13118

NHRI > National Institute of Infectious Diseases and Vaccinology > Chia-Yi Yu > Periodical Articles > Item 3990099045/13118

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/13118

Title:	Dengue nonstructural protein 1 maintains autophagy through retarding caspase-mediated cleavage of beclin-1
Authors:	Lu, ZY;Cheng, MH;Yu, CY;Lin, YS;Yeh, TM;Chen, CL;Chen, CC;Wan, SW;Chang, CP
Contributors:	National Institute of Infectious Diseases and Vaccinology
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.
Date:	2020-12-19
Relation:	International Journal of Molecular Sciences. 2020 Dec 19;21(24):Article number 9702.
Link to:	http://dx.doi.org/10.3390/ijms21249702
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1422-0067&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000602761000001
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85098158944
Appears in Collections:	[Chia-Yi Yu] Periodical Articles

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