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:
- The ATGL lipase cooperates with ABHD5 to mobilize lipids for hepatitis C virus assembly.
- Authors: Vieyres G, Reichert I, Carpentier A, Vondran FWR, Pietschmann T
- Issue date: 2020 Jun
- Molecular mechanism of the ichthyosis pathology of Chanarin-Dorfman syndrome: Stimulation of PNPLA1-catalyzed ω-O-acylceramide production by ABHD5.
- Authors: Ohno Y, Nara A, Nakamichi S, Kihara A
- Issue date: 2018 Dec
- 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
- 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
- Thyroid involvement in Chanarin-Dorfman syndrome in adults in the largest series of patients carrying the same founder mutation in ABHD5 gene.
- Authors: Louhichi N, Bahloul E, Marrakchi S, Othman HB, Triki C, Aloulou K, Trabelsi L, Mahfouth N, Ayadi-Mnif Z, Keskes L, Fakhfakh F, Turki H
- Issue date: 2019 May 22