TIM-1 As a Signal Receptor Triggers Dengue Virus-Induced Autophagy

• Published in: International journal of molecular sciences Vol. 20; no. 19; p. 4893
• Main Authors: Chu, Li-Wei, Yang, Chia-Jui, Peng, Kuan-Jen, Chen, Pei-Ling, Wang, Shuu-Jiun, Ping, Yueh-Hsin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.10.2019; MDPI
• Subjects: Antibodies; Autophagosomes - metabolism; Autophagy; Binding sites; Biomarkers; Cell Line; Dengue - metabolism; Dengue - virology; Dengue fever; Dengue Virus; Flow cytometry; Gene Knockdown Techniques; Genomes; Hepatitis A; Hepatitis A Virus Cellular Receptor 1 - metabolism; Humans; Immunoglobulins; Infections; Kinases; Models, Biological; Pathogens; Proteins; Roles; Signal Transduction; Viral infections; Virus Replication; Viruses; West Nile virus; early endosome; autophagy; p85; TIM-1; dengue virus; rab5
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20194893

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.