Dengue virus autophagy

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We further manipulated DV-induced autophagy by the inducer rapamycin and the inhibitor 3-methyladenine 3MA , which accordingly promoted or suppressed the disease symptoms and virus load in the brain of the infected mice. Early after infection, basal and activated autophagic flux was enhanced.

However, during established replication, basal and Torin1-activated autophagic flux was blocked, while autophagic flux activated by nutrient deprivation was reduced, indicating a block to AV formation and reduced AV degradation capacity. During late infection AV levels increased as a result of inefficient fusion of autophagosomes with lysosomes.

In addition, endolysosomal trafficking was suppressed, while lysosomal activities were increased. Importantly, stable overexpression of p62 significantly suppressed DENV replication, suggesting a novel role for p62 as a viral restriction factor.

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This article has been cited by other articles in PMC. Abstract A virus that reproduces in a host without killing cells can easily establish a successful infection. Results ER stress signaling, activated during infection, is required for virus-induced autophagy, protection of cells and production of virus Flavivirus including dengue are ER tropic and cause the ER to initiate stress response signaling.

Open in a separate window. Figure 1. Figure 2. Figure 3. Figure 4. At later stages of infection, PERK-dependent ROS accumulation is important for induction of autophagy Activation of autophagy can be associated with the production of ROS and increased ER stress; 19 and oxidative stress has been observed in dengue-infected cells. Figure 5. Figure 6. Discussion Infection activates ATM kinase that induces autophagy, leading to protection from toxins How dengue virus regulates autophagy is poorly understood.

Induction of the ER stress, especially the PERK pathway, is central to a high autophagy turnover in infected mammalian cells Infection and viral reproduction partially depend on the metabolic and synthetic processes in the infected cells, 53 , 55 , 56 including translation of dengue protein in the ER and dengue-induced alterations of the ER-Golgi network. Activation of ATM kinase, and subsequent PERK activation, integrates with autophagy to protect cells from toxic assaults The inhibition of ATM and subsequent autophagy by caffeine and KU results in the loss of dengue-induced protection against other stressors.

Assessment of cell viability Cells were infected and exposed to toxin i. Western blot, immunocytochemistry and cytochemistry Cells were infected and treated as described above.

Acknowledgments We thank Dr. Notes The authors declare no conflict of interest. Footnotes Edited by M Piacentini. First two autochthonous dengue virus infections in metropolitan France, September Euro surveill ; 15 : Dengue fever: new paradigms for a changing epidemiology. Emerg Themes Epidemiol ; 2 : 1. Dengue virus infection of human endothelial cells leads to chemokine production, complement activation, and apoptosis.

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