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Dengue Nonstructural Protein 1 Maintains Autophagy through Retarding Caspase-Mediated Cleavage of Beclin-1
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 au...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766445/ https://www.ncbi.nlm.nih.gov/pubmed/33352639 http://dx.doi.org/10.3390/ijms21249702 |
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author | 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 |
author_facet | 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 |
author_sort | Lu, Zi-Yi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7766445 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77664452020-12-28 Dengue Nonstructural Protein 1 Maintains Autophagy through Retarding Caspase-Mediated Cleavage of Beclin-1 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 Int J Mol Sci Article 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. MDPI 2020-12-19 /pmc/articles/PMC7766445/ /pubmed/33352639 http://dx.doi.org/10.3390/ijms21249702 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article 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 Dengue Nonstructural Protein 1 Maintains Autophagy through Retarding Caspase-Mediated Cleavage of Beclin-1 |
title | Dengue Nonstructural Protein 1 Maintains Autophagy through Retarding Caspase-Mediated Cleavage of Beclin-1 |
title_full | Dengue Nonstructural Protein 1 Maintains Autophagy through Retarding Caspase-Mediated Cleavage of Beclin-1 |
title_fullStr | Dengue Nonstructural Protein 1 Maintains Autophagy through Retarding Caspase-Mediated Cleavage of Beclin-1 |
title_full_unstemmed | Dengue Nonstructural Protein 1 Maintains Autophagy through Retarding Caspase-Mediated Cleavage of Beclin-1 |
title_short | Dengue Nonstructural Protein 1 Maintains Autophagy through Retarding Caspase-Mediated Cleavage of Beclin-1 |
title_sort | dengue nonstructural protein 1 maintains autophagy through retarding caspase-mediated cleavage of beclin-1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766445/ https://www.ncbi.nlm.nih.gov/pubmed/33352639 http://dx.doi.org/10.3390/ijms21249702 |
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