Dengue virus infection perturbs lipid homeostasis in infected mosquito cells

Rushika Perera, Catherine Riley, Giorgis Isaac, Amber S. Hopf-Jannasch, Ronald J. Moore, Karl W. Weitz, Ljiljana Pasa-Tolic, Thomas O. Metz, Jiri Adamec, Richard J. Kuhn

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

Dengue virus causes ~50-100 million infections per year and thus is considered one of the most aggressive arthropod-borne 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 membrane-organizing principles that may influence virus-induced intracellular membrane architecture.

Original languageEnglish (US)
Article numbere1002584
JournalPLoS pathogens
Volume8
Issue number3
DOIs
StatePublished - Mar 1 2012

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Dengue Virus
Virus Diseases
Culicidae
Homeostasis
Lipids
Intracellular Membranes
Membranes
Fatty Acid Synthases
Sphingolipids
Membrane Fusion
Dengue
Arthropods
Virus Replication
Infection
Permeability
Mass Spectrometry
Cell Survival
Membrane Proteins
Cell Membrane
Viruses

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Perera, R., Riley, C., Isaac, G., Hopf-Jannasch, A. S., Moore, R. J., Weitz, K. W., ... Kuhn, R. J. (2012). Dengue virus infection perturbs lipid homeostasis in infected mosquito cells. PLoS pathogens, 8(3), [e1002584]. https://doi.org/10.1371/journal.ppat.1002584

Dengue virus infection perturbs lipid homeostasis in infected mosquito cells. / Perera, Rushika; Riley, Catherine; Isaac, Giorgis; Hopf-Jannasch, Amber S.; Moore, Ronald J.; Weitz, Karl W.; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Adamec, Jiri; Kuhn, Richard J.

In: PLoS pathogens, Vol. 8, No. 3, e1002584, 01.03.2012.

Research output: Contribution to journalArticle

Perera, R, Riley, C, Isaac, G, Hopf-Jannasch, AS, Moore, RJ, Weitz, KW, Pasa-Tolic, L, Metz, TO, Adamec, J & Kuhn, RJ 2012, 'Dengue virus infection perturbs lipid homeostasis in infected mosquito cells', PLoS pathogens, vol. 8, no. 3, e1002584. https://doi.org/10.1371/journal.ppat.1002584
Perera R, Riley C, Isaac G, Hopf-Jannasch AS, Moore RJ, Weitz KW et al. Dengue virus infection perturbs lipid homeostasis in infected mosquito cells. PLoS pathogens. 2012 Mar 1;8(3). e1002584. https://doi.org/10.1371/journal.ppat.1002584
Perera, Rushika ; Riley, Catherine ; Isaac, Giorgis ; Hopf-Jannasch, Amber S. ; Moore, Ronald J. ; Weitz, Karl W. ; Pasa-Tolic, Ljiljana ; Metz, Thomas O. ; Adamec, Jiri ; Kuhn, Richard J. / Dengue virus infection perturbs lipid homeostasis in infected mosquito cells. In: PLoS pathogens. 2012 ; Vol. 8, No. 3.
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