Dengue virus induces mitochondrial elongation through impairment of Drp1-triggered mitochondrial fission.
Mitochondria are highly dynamic organelles that undergo continuous cycles of fission and fusion to maintain essential cellular functions. An imbalance between these two processes can result in many pathophysiological outcomes. Dengue virus (DENV) interacts with cellular organelles, including mitochondria, to successfully replicate in cells. This study used live-cell imaging and found an increase in mitochondrial length and respiration during DENV infection. The level of mitochondrial fission protein, Dynamin-related protein 1 (Drp1), was decreased on mitochondria during DENV infection, as well as Drp1 phosphorylated on serine 616, which is important for mitochondrial fission. DENV proteins NS4b and NS3 were also associated with subcellular fractions of mitochondria. Induction of fission through uncoupling of mitochondria or overexpression of Drp1 wild-type and Drp1 with a phosphomimetic mutation (S616D) significantly reduced viral replication. These results demonstrate that DENV infection causes an imbalance in mitochondrial dynamics by inhibiting Drp1-triggered mitochondrial fission, which promotes viral replication.
Institute for Immunology and Informatics, Department of Cell and Molecular Biology, University of Rhode Island, Providence, RI 02903, United States.
Vincent
V
Barbier
Institute for Immunology and Informatics, Department of Cell and Molecular Biology, University of Rhode Island, Providence, RI 02903, United States.
Diane
D
Lang
Institute for Immunology and Informatics, Department of Cell and Molecular Biology, University of Rhode Island, Providence, RI 02903, United States.
Sierra
S
Valois
Institute for Immunology and Informatics, Department of Cell and Molecular Biology, University of Rhode Island, Providence, RI 02903, United States.
Alan L
AL
Rothman
Institute for Immunology and Informatics, Department of Cell and Molecular Biology, University of Rhode Island, Providence, RI 02903, United States. Electronic address: cmedin.uri@gmail.com.
Carey L
CL
Medin
D020816:Amino Acid Motifs; D002460:Cell Line; D003715:Dengue / Q000378:metabolism* / Q000503:physiopathology* / Q000821:virology; D003716:Dengue Virus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism* / Q000821:virology; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism
D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D017361:Viral Nonstructural Proteins; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins
Dendritic cells; Dengue virus; Drp1; Fission; Fusion; Live-cell imaging; Mitochondria