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Updated: Jun 8, 2025
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A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease
Published on: April 28, 2019
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Targeting PI3Kγ Pathway for Treating Dengue virus Infection
Felipe R da S Santos1, Deborah F Valadão2, Jordana L Bambirra2
1Departament of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Departament of Morphology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Microbial Pathogenesis
|November 4, 2024
Summary
Inhibiting PI3Kγ reduces Dengue virus (DENV) severity by controlling inflammation and viral load. This finding highlights PI3Kγ as a potential therapeutic target for Dengue disease treatment.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- Dengue virus (DENV) infection causes significant global health issues with no specific treatments.
- DENV pathogenesis involves complex viral and host factors, notably an excessive inflammatory response.
- Viruses, including DENV, can modulate the PI3K/Akt signaling pathway, but mechanisms are unclear.
Purpose of the Study:
- To investigate the role of PI3Kγ in DENV infection in vivo.
- To evaluate the therapeutic potential of PI3Kγ inhibition against DENV.
Main Methods:
- Experiments utilized wild-type and PI3Kγ knockout mice infected with DENV.
- Evaluated parameters included survival, hematology, virology, histopathology, and inflammation.
- Assessed the efficacy of a selective PI3Kγ inhibitor (AS605240) in DENV-infected mice.
Main Results:
- PI3Kγ deficiency reduced DENV lethality, thrombocytopenia, hemoconcentration, vascular permeability, and liver damage.
- Reduced viral replication and inflammatory mediator production (e.g., IL-6) were observed in PI3Kγ-deficient mice.
- Pharmacologic inhibition of PI3Kγ ameliorated DENV symptoms and decreased viral load.
Conclusions:
- The PI3Kγ signaling pathway promotes DENV infection and pathogenesis by exacerbating inflammation.
- PI3Kγ inhibition is a promising host-directed strategy for novel Dengue disease therapies.
