Abstract
Simple SummaryDengue is an important and growing public health problem. To date, no specific therapeutic or effective prophylactic measures exist. Therefore, vector control remains the primary approach to prevent dengue virus (DENV) infection in humans. Recent findings highlight that viruses regulate mitochondrial function and dynamics to facilitate viral proliferation. In this study, we report that DENV infection modulates mitochondrial physiology in C6/36 mosquito cells. Our results revealed that DENV alters redox metabolism and mitochondrial membrane potential without any significant change in cellular ATP pool or viability. In addition, we observed preservation of the respiratory control ratio and translocation of mitofusins to mitochondria. These results suggest that mitochondrial fusion could be required for the maintenance of mitochondrial function in C6/36 mosquito cells infected with DENV.Aedes aegypti and Aedes albopictus mosquitoes are responsible for dengue virus (DENV) transmission in tropical and subtropical areas worldwide, where an estimated 3 billion people live at risk of DENV exposure. DENV-infected individuals show symptoms ranging from sub-clinical or mild to hemorrhagic fever. Infected mosquitoes do not show detectable signs of disease, even though the virus maintains a lifelong persistent infection. The interactions between viruses and host mitochondria are crucial for virus replication and pathogenicity. DENV infection in vertebrate cells modulates mitochondrial function and dynamics to facilitate viral proliferation. Here, we describe that DENV also regulates mitochondrial function and morphology in infected C6/36 mosquito cells (derived from Aedes albopictus). Our results showed that DENV infection increased ROS (reactive oxygen species) production, modulated mitochondrial transmembrane potential and induced changes in mitochondrial respiration. Furthermore, we offer the first evidence that DENV causes translocation of mitofusins to mitochondria in the C6/36 mosquito cell line. Another protein Drp-1 (Dynamin-related protein 1) did not localize to mitochondria in DENV-infected cells. This observation therefore ruled out the possibility that the abovementioned alterations in mitochondrial function are associated with mitochondrial fission. In summary, this report provides some key insights into the virus–mitochondria crosstalk in DENV infected mosquito cells.
Highlights
Mitochondria are highly dynamic and inter-connected organelles that regulate a variety of cellular processes including energy homeostasis, redox status, thermogenesis, and cell death via apoptosis [1]
To assess if mitochondrial dynamics changed during DENV2 infection in mosquito C6/36 cells, we evaluated the localization of Dynamin-related protein 1 (Drp1) and MFNs, proteins involved in mitochondrial fission and fusion, respectively
Despite the importance of hematophagous female mosquitoes Aedes spp. as a vector of different arboviruses including dengue virus (DENV), most of our knowledge on dengue biology comes from studies in mammalian cells and limited work has been conducted in mosquitoes
Summary
Mitochondria are highly dynamic and inter-connected organelles that regulate a variety of cellular processes including energy homeostasis, redox status, thermogenesis, and cell death via apoptosis [1]. Following RNA replication, synthesis of the viral proteins and immature virions are assembled inside the lumen of the ER During this process, the virus particles obtain their enveloped, mature lipid bilayer by passing through the Golgi and trans-Golgi network. DENV infection modulates mitochondrial dynamics in mammalian cells to regulate the innate immune signaling and promote virus replication. In hepatic cells (Huh-7), DENV protein NS4B induced mitochondrial elongation due to a reduction in Drp protein levels in mitochondria [12,13]; DENV produces an increase in cellular respiration and decreases ATP production [14]. We offer the first evidence that DENV induces the translocation of mitofusins (MFNs) to mitochondria
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