Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells

Authors

Rushika Perera, Purdue University
Catherine Riley, Purdue University
Giorgis Isaac, Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington
Amber S. Hopf-Jannasch, Purdue University
Ronald J. Moore, Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington
Karl W. Weitz, Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington
Ljiljana Pasa-Tolic, Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington
Thomas O. Metz, Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington
Jiri Adamec, University of Nebraska-LincolnFollow
Richard J. Kuhn, Purdue UniversityFollow

Document Type

Article

Date of this Version

2012

Citation

Perera R, Riley C, Isaac G, Hopf-Jannasch AS, Moore RJ, et al. (2012) Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells. PLoS Pathog 8(3): e1002584.

Comments

Copyright 2012 Perera et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License.

Abstract

Dengue virus causes ~50–100 million infections per year and thus is considered one of the most aggressive arthropodborne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membraneorganizing principles that may influence virus-induced intracellular membrane architecture.