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Cellular Oxidative Stress Response Controls the Antiviral and Apoptotic Programs in Dengue Virus-Infected Dendritic Cells


Dengue virus (DENV), the leading arthropod-borne viral infection in the world, represents a major human health concern with a global at risk population of over 3 billion people. Currently, there are no antivirals or vaccines available to treat patients with dengue fever, nor is it possible to predict which patients will progress to life-threatening severe dengue fever. Markers associated with oxidative stress responses have been reported in patients with severe DENV infection, suggesting a relationship between oxidative stress and viral pathogenesis. In order to uncover biological processes that determine the outcome of disease in patients, we utilized human dendritic cells, the primary target of DENV infection, in an in vitro model. Transcriptional analysis of pathways activated upon de novo DENV infection revealed a major role for cellular oxidative stress in the induction of antiviral, inflammatory, and cell death responses. We also demonstrated that antioxidant mechanisms play a critical role in controlling antiviral and cell death responses to the virus, acting as feedback regulators of the oxidative stress response. This report highlights the importance of oxidative stress responses in the outcome of DENV infection, and identifies this pathway as a potential new entry-point for treating dengue-associated diseases.


Vyšlo v časopise: Cellular Oxidative Stress Response Controls the Antiviral and Apoptotic Programs in Dengue Virus-Infected Dendritic Cells. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004566
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004566

Souhrn

Dengue virus (DENV), the leading arthropod-borne viral infection in the world, represents a major human health concern with a global at risk population of over 3 billion people. Currently, there are no antivirals or vaccines available to treat patients with dengue fever, nor is it possible to predict which patients will progress to life-threatening severe dengue fever. Markers associated with oxidative stress responses have been reported in patients with severe DENV infection, suggesting a relationship between oxidative stress and viral pathogenesis. In order to uncover biological processes that determine the outcome of disease in patients, we utilized human dendritic cells, the primary target of DENV infection, in an in vitro model. Transcriptional analysis of pathways activated upon de novo DENV infection revealed a major role for cellular oxidative stress in the induction of antiviral, inflammatory, and cell death responses. We also demonstrated that antioxidant mechanisms play a critical role in controlling antiviral and cell death responses to the virus, acting as feedback regulators of the oxidative stress response. This report highlights the importance of oxidative stress responses in the outcome of DENV infection, and identifies this pathway as a potential new entry-point for treating dengue-associated diseases.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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