TIM-1 As a Signal Receptor Triggers Dengue Virus-Induced Autophagy
Dengue virus (DENV) infection triggers the activation of autophagy to facilitate the viral replication cycle from various aspects. Although a number of stimulators are proposed to activate autophagy, none of them appears prior to the uncoating process. Given that T-cell immunoglobulin and mucin doma...
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doaj-54f02badfb5a47c4be8b9672363477862020-11-25T01:58:27ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-10-012019489310.3390/ijms20194893ijms20194893TIM-1 As a Signal Receptor Triggers Dengue Virus-Induced AutophagyLi-Wei Chu0Chia-Jui Yang1Kuan-Jen Peng2Pei-Ling Chen3Shuu-Jiun Wang4Yueh-Hsin Ping5Institute of Biophotonics, National Yang-Ming University, Taipei 11221, TaiwanFaculty of Medicine, National Yang-Ming University, Taipei 11221, TaiwanDepartment and Institute of Pharmacology, National Yang-Ming University, Taipei 11221, TaiwanDepartment and Institute of Pharmacology, National Yang-Ming University, Taipei 11221, TaiwanBrain Research Center, National Yang-Ming University, Taipei 11221, TaiwanInstitute of Biophotonics, National Yang-Ming University, Taipei 11221, TaiwanDengue virus (DENV) infection triggers the activation of autophagy to facilitate the viral replication cycle from various aspects. Although a number of stimulators are proposed to activate autophagy, none of them appears prior to the uncoating process. Given that T-cell immunoglobulin and mucin domain 1 (TIM-1) receptor is a putative DENV receptor and promotes apoptotic body clearance by autophagy induction, it raises the possibility that TIM-1 may participate in the activation of DENV-induced autophagy. In this study, confocal images first revealed the co-localization of TIM-1 with autophagosomes in DENV-induced autophagy rather than rapamycin-induced autophagy, suggesting the co-transportation of TIM-1 with DENV during infection. The treatment of siRNA to knockdown TIM-1 expression in DENV-infected GFP-microtubule-associated protein light chain 3 (LC3)-Huh7.5 cells revealed that TIM-1 is required not only for DENV cellular internalization but also for autophagy activation. Furthermore, knockdown p85, a subunit of phosphoinositide 3-kinases (PI3Ks), which is co-localized with TIM-1 at rab5-positive endosomes caused the reduction of autophagy, indicating that TIM-1-mediated DENV-induced autophagy requires p85. Taken together, the current study uncovered TIM-1 as a novel factor for triggering autophagy in DENV infection through TIM-1-p85 axis, in addition to serving as a DENV receptor.https://www.mdpi.com/1422-0067/20/19/4893dengue virusautophagytim-1p85rab5early endosome |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Li-Wei Chu Chia-Jui Yang Kuan-Jen Peng Pei-Ling Chen Shuu-Jiun Wang Yueh-Hsin Ping |
spellingShingle |
Li-Wei Chu Chia-Jui Yang Kuan-Jen Peng Pei-Ling Chen Shuu-Jiun Wang Yueh-Hsin Ping TIM-1 As a Signal Receptor Triggers Dengue Virus-Induced Autophagy International Journal of Molecular Sciences dengue virus autophagy tim-1 p85 rab5 early endosome |
author_facet |
Li-Wei Chu Chia-Jui Yang Kuan-Jen Peng Pei-Ling Chen Shuu-Jiun Wang Yueh-Hsin Ping |
author_sort |
Li-Wei Chu |
title |
TIM-1 As a Signal Receptor Triggers Dengue Virus-Induced Autophagy |
title_short |
TIM-1 As a Signal Receptor Triggers Dengue Virus-Induced Autophagy |
title_full |
TIM-1 As a Signal Receptor Triggers Dengue Virus-Induced Autophagy |
title_fullStr |
TIM-1 As a Signal Receptor Triggers Dengue Virus-Induced Autophagy |
title_full_unstemmed |
TIM-1 As a Signal Receptor Triggers Dengue Virus-Induced Autophagy |
title_sort |
tim-1 as a signal receptor triggers dengue virus-induced autophagy |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-10-01 |
description |
Dengue virus (DENV) infection triggers the activation of autophagy to facilitate the viral replication cycle from various aspects. Although a number of stimulators are proposed to activate autophagy, none of them appears prior to the uncoating process. Given that T-cell immunoglobulin and mucin domain 1 (TIM-1) receptor is a putative DENV receptor and promotes apoptotic body clearance by autophagy induction, it raises the possibility that TIM-1 may participate in the activation of DENV-induced autophagy. In this study, confocal images first revealed the co-localization of TIM-1 with autophagosomes in DENV-induced autophagy rather than rapamycin-induced autophagy, suggesting the co-transportation of TIM-1 with DENV during infection. The treatment of siRNA to knockdown TIM-1 expression in DENV-infected GFP-microtubule-associated protein light chain 3 (LC3)-Huh7.5 cells revealed that TIM-1 is required not only for DENV cellular internalization but also for autophagy activation. Furthermore, knockdown p85, a subunit of phosphoinositide 3-kinases (PI3Ks), which is co-localized with TIM-1 at rab5-positive endosomes caused the reduction of autophagy, indicating that TIM-1-mediated DENV-induced autophagy requires p85. Taken together, the current study uncovered TIM-1 as a novel factor for triggering autophagy in DENV infection through TIM-1-p85 axis, in addition to serving as a DENV receptor. |
topic |
dengue virus autophagy tim-1 p85 rab5 early endosome |
url |
https://www.mdpi.com/1422-0067/20/19/4893 |
work_keys_str_mv |
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1724969521339432960 |