Dengue virion:HAVCR1 induces autophagosome formation

Stable Identifier
R-HSA-9945936
Type
Reaction [uncertain]
Species
Homo sapiens
Related Species
Dengue virus type 2
Compartment
autophagosome membrane, endosome membrane
ReviewStatus
5/5
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Dengue virion:HAVCR1 induces autophagosome formation
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DENV-containing endosomes deliver DENV to autophagosomes (Chu et al., 2014; Chu et al., 2019). In human Huh7.5 cells infected with DENV-2 (strain 16681), formation of these vesicles is triggered by binding of HAVCR1 (TIM1, TIM-1) to Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1, p85) with subsequent activation of the PI3K pathway (Chu et al., 2019). This also induces a type of selective autophagy termed lipophagy which supports DENV replication (reviewed in Heaton & Randall, 2011; Echavarria-Consuegra et al., 2019). Both lysophagosomes and lipophagosomes feature low pH environments (reviewed in Shin et al., 2020). However, it is unclear if DENV virions in autophagosomes fuse with their membrane to release viral RNA. In DENV-2 infected human A549 cells, triggering of virus-propagating autophagy pathways requires High mobility group protein B1 (HMGB1), which can be inhibited by glycyrrhizin (Chaudhary et al., 2023). Autophagy induction also involves the host E3 ligase TRIM22, as demonstrated in DENV-2 (NGC strain) infection of human HUVEC cells (Wu et al., 2022).
Literature References
PubMed ID Title Journal Year
24192777 Single-virus tracking approach to reveal the interaction of Dengue virus with autophagy during the early stage of infection

Chu, LW, Huang, YL, Lee, JH, Huang, LY, Chen, WJ, Lin, YH, Chen, JY, Xiang, R, Lee, CH, Ping, YH

J Biomed Opt 2014
31581681 TIM-1 As a Signal Receptor Triggers Dengue Virus-Induced Autophagy

Chu, LW, Yang, CJ, Peng, KJ, Chen, PL, Wang, SJ, Ping, YH

Int J Mol Sci 2019
36587643 Dengue virus induced autophagy is mediated by HMGB1 and promotes viral propagation

Chaudhary, N, Srivastava, S, Gupta, S, Menon, MB, Patel, AK

Int J Biol Macromol 2023
30862253 Role of autophagy during the replication and pathogenesis of common mosquito-borne flavi- and alphaviruses

Echavarria-Consuegra, L, Smit, JM, Reggiori, F

Open Biol 2019
21994782 Dengue virus and autophagy

Heaton, NS, Randall, G

Viruses 2011
36587218 Mechanism of autophagy induced by activation of the AMPK/ERK/mTOR signaling pathway after TRIM22-mediated DENV-2 infection of HUVECs

Wu, N, Gou, X, Hu, P, Chen, Y, Ji, J, Wang, Y, Zuo, L

Virol J 2022
32624503 Lipophagy: Molecular Mechanisms and Implications in Metabolic Disorders

Shin, DW

Mol Cells 2020
40270809 Orthoflavivirus infection and the mTOR signaling pathway

Zhang, Y, Ba, J, Luan, J, Qi, Z, Liu, B

Front Microbiol 2025
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Output
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as an event of
Event Information
Go Biological Process
autophagosome-endosome fusion (0061910)
This event is regulated
Requirements
Disease
Name Identifier Synonyms
dengue disease DOID:12205 breakbone fever, Dengue Fever, classic dengue
Cross References
Mondo
Authored
Stephan, R  (2025-04-19)
Reviewed
Mansur, DS  (2025-10-29)
Roque Ascenção, F  (2025-10-29)
Created
Stephan, R  (2025-04-20)
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