Dengue virus non-structural protein 3 inhibits mitochondrial respiration by impairing complex I function.
Bruna G SousaNathane C Mebus-AntunesLorena O Fernandes-SiqueiraMarjolly B CarusoGeorgia N SaraivaClara F CarvalhoThais C Neves-MartinsAntonio GalinaRussolina B ZingaliJulianna D ZeidlerAndrea T Da PoianPublished in: mSphere (2024)
Dengue virus (DENV) infection is a major public health problem worldwide, affecting about 400 million people yearly. Despite its importance, many molecular aspects of dengue pathogenesis remain poorly known. For several years, our group has been investigating DENV-induced metabolic alterations in the host cells, focusing on the bioenergetics of mitochondrial respiration. The results of the present study reveal that the DENV non-structural protein 3 (NS3) is found in the mitochondria of infected cells, impairing mitochondrial respiration by directly targeting one of the components of the electron transport system, the respiratory complex I (CI). NS3 acts as the viral protease during the DENV replication cycle, and its proteolytic activity seems necessary for inhibiting CI function. Our findings uncover new nuances of DENV-induced metabolic alterations, highlighting NS3 as an important player in the modulation of mitochondria function during infection.
Keyphrases
- dengue virus
- zika virus
- induced apoptosis
- aedes aegypti
- oxidative stress
- public health
- cell cycle arrest
- diabetic rats
- cell death
- high glucose
- signaling pathway
- sars cov
- drug induced
- protein protein
- binding protein
- endothelial cells
- amino acid
- genome wide
- endoplasmic reticulum stress
- dna methylation
- pi k akt
- drug delivery