TIM-1 as a signal receptor triggers dengue virus-induced autophagy

Li Wei Chu, Chia Jui Yang, Kuan Jen Peng, Pei Ling Chen, Shuu Jiun Wang, Yueh Hsin Ping*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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.

Original languageEnglish
Article number4893
JournalInternational Journal Of Molecular Sciences
Issue number19
StatePublished - 1 Oct 2019


  • Autophagy
  • Dengue virus
  • Early endosome
  • P85
  • Rab5
  • TIM-1


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