ABHD5/CGI-58, the Chanarin-Dorfman Syndrome Protein, Mobilises Lipid Stores for Hepatitis C Virus Production.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Vondran, Florian W R
MetadataShow full item record
AbstractHepatitis C virus (HCV) particles closely mimic human very-low-density lipoproteins (VLDL) to evade humoral immunity and to facilitate cell entry. However, the principles that govern HCV association with VLDL components are poorly defined. Using an siRNA screen, we identified ABHD5 (α/β hydrolase domain containing protein 5, also known as CGI-58) as a new host factor promoting both virus assembly and release. ABHD5 associated with lipid droplets and triggered their hydrolysis. Importantly, ABHD5 Chanarin-Dorfman syndrome mutants responsible for a rare lipid storage disorder in humans were mislocalised, and unable to consume lipid droplets or support HCV production. Additional ABHD5 mutagenesis revealed a novel tribasic motif that does not influence subcellular localization but determines both ABHD5 lipolytic and proviral properties. These results indicate that HCV taps into the lipid droplet triglyceride reservoir usurping ABHD5 lipase cofactor function. They also suggest that the resulting lipid flux, normally devoted to VLDL synthesis, also participates in the assembly and release of the HCV lipo-viro-particle. Altogether, our study provides the first association between the Chanarin-Dorfman syndrome protein and an infectious disease and sheds light on the hepatic manifestations of this rare genetic disorder as well as on HCV morphogenesis.
CitationABHD5/CGI-58, the Chanarin-Dorfman Syndrome Protein, Mobilises Lipid Stores for Hepatitis C Virus Production. 2016, 12 (4):e1005568 PLoS Pathog.
AffiliationTwincore Centre for Experimental and Clinical Infection Research, Hannover, Germany.
The following license files are associated with this item:
- Critical roles for α/β hydrolase domain 5 (ABHD5)/comparative gene identification-58 (CGI-58) at the lipid droplet interface and beyond.
- Authors: Brown AL, Mark Brown J
- Issue date: 2017 Oct
- Early onset of Chanarin-Dorfman syndrome with severe liver involvement in a patient with a complex rearrangement of ABHD5 promoter.
- Authors: Missaglia S, Valadares ER, Moro L, Faguntes ED, Quintão Roque R, Giardina B, Tavian D
- Issue date: 2014 Mar 14
- An exceptional mutational event leading to Chanarin-Dorfman syndrome in a large consanguineous family.
- Authors: Samuelov L, Fuchs-Telem D, Sarig O, Sprecher E
- Issue date: 2011 Jun
- The important role of epidermal triacylglycerol metabolism for maintenance of the skin permeability barrier function.
- Authors: Radner FP, Fischer J
- Issue date: 2014 Mar
- Chanarin-Dorfman syndrome: a novel mutation in a Turkish girl.
- Authors: Ünlüsoy-Aksu A, Sarı S, Eğritaş-Gürkan Ö, Dalgıç B
- Issue date: 2015 May-Jun