The antiviral protein, viperin, localizes to lipid droplets via its N-terminal amphipathic α-helix
- 1 December 2009
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 106 (48), 20452-20457
- https://doi.org/10.1073/pnas.0911679106
Abstract
Lipid droplets are intracellular lipid-storage organelles that are thought to be derived from the endoplasmic reticulum (ER). Several pathogens, notably hepatitis C virus, use lipid droplets for replication. Numerous questions remain about how lipid droplets are generated and used by viruses. Here we show that the IFN-induced antiviral protein viperin, which localizes to the cytosolic face of the ER and inhibits HCV, localizes to lipid droplets. We show that the N-terminal amphipathic α-helix of viperin that is responsible for ER localization is also necessary and sufficient to localize both viperin and the fluorescent protein dsRed to lipid droplets. Point mutations in the α-helix that prevent ER association also disrupt lipid droplet association, and sequential deletion mutants indicate that the same number of helical turns are necessary for ER and lipid droplet association. Finally, we show that the N-terminal amphipathic α-helix of the hepatitis C viral protein NS5A can localize dsRed and viperin to lipid droplets. These findings indicate that the amphipathic α-helices of viperin and NS5A are lipid droplet-targeting domains and suggest that viperin inhibits HCV by localizing to lipid droplets using a domain and mechanism similar to that used by HCV itself.Keywords
This publication has 21 references indexed in Scilit:
- The N-terminal Amphipathic α-Helix of Viperin Mediates Localization to the Cytosolic Face of the Endoplasmic Reticulum and Inhibits Protein SecretionPublished by Elsevier BV ,2009
- Hepatitis C Virus Core Protein Induces Lipid Droplet Redistribution in a Microtubule‐ and Dynein‐Dependent MannerTraffic, 2008
- Lipid droplets: a classic organelle with new outfitsHistochemistry and Cell Biology, 2008
- Identification of Three Interferon-Inducible Cellular Enzymes That Inhibit the Replication of Hepatitis C VirusJournal of Virology, 2008
- The lipid droplet is an important organelle for hepatitis C virus productionNature, 2007
- The Interferon-Inducible Protein Viperin Inhibits Influenza Virus Release by Perturbing Lipid RaftsCell Host & Microbe, 2007
- Role of the hydrophobic domain in targeting caveolin-1 to lipid dropletsThe Journal of cell biology, 2004
- Amphipathic Helix-Dependent Localization of NS5A Mediates Hepatitis C Virus RNA ReplicationJournal of Virology, 2003
- An Amino-terminal Amphipathic α-Helix Mediates Membrane Association of the Hepatitis C Virus Nonstructural Protein 5AJournal of Biological Chemistry, 2002
- Caveolin-2 Is Targeted to Lipid Droplets, a New “Membrane Domain” in the CellThe Journal of cell biology, 2001