Dengue virus reduces expression of low-density lipoprotein receptor-related protein 1 to facilitate replication in Aedes aegypti.
Maya O TreeBerlin Londono-RenteríaAndrea TroupinKellie M ClarkTonya M ColpittsMichael J ConwayPublished in: Scientific reports (2019)
Aedes aegypti is the primary vector of a number of viruses pathogenic to humans including dengue virus (DENV). DENV infection leads to widespread transcriptomic and proteomic alterations in mosquito cells. Here we identified alterations to the mosquito cell secretome during DENV infection by performing liquid chromatography tandem mass spectrometry. We found that an extracellular fragment of low-density lipoprotein receptor-related protein 1 (LRP-1) was present during infection. Previous literature suggests that LRP-1 regulates cholesterol homeostasis. Therefore, we hypothesized that DENV modifies LRP-1 protein expression to maintain host-derived intracellular cholesterol, which would facilitate virus replication within membrane-associated replication compartments. Accordingly, stimuli that are present during flavivirus infection reduced LRP-1 protein expression. We also found that dsRNA knockdown of LRP-1 increased intracellular cholesterol and DENV viral RNA. Further, depletion of intracellular lipids reduced infection. Together, these data suggest that DENV reduces LRP-1 protein expression, possibly through regulated intramembrane proteolysis (RIP), to increase intracellular cholesterol and facilitate replication in Ae. aegypti.
Keyphrases
- dengue virus
- low density lipoprotein
- aedes aegypti
- zika virus
- liquid chromatography tandem mass spectrometry
- reactive oxygen species
- systematic review
- sars cov
- single cell
- stem cells
- ms ms
- machine learning
- mass spectrometry
- induced apoptosis
- cell proliferation
- deep learning
- cell death
- mesenchymal stem cells
- cell therapy
- nucleic acid