ABHD5/CGI-58, the Chanarin-Dorfman Syndrome Protein, Mobilises Lipid Stores for Hepatitis C Virus Production.

2.50
Hdl Handle:
http://hdl.handle.net/10033/607736
Title:
ABHD5/CGI-58, the Chanarin-Dorfman Syndrome Protein, Mobilises Lipid Stores for Hepatitis C Virus Production.
Authors:
Vieyres, Gabrielle; Welsch, Kathrin; Gerold, Gisa; Gentzsch, Juliane; Kahl, Sina; Vondran, Florian W R; Kaderali, Lars; Pietschmann, Thomas
Abstract:
Hepatitis 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.
Affiliation:
Twincore Centre for Experimental and Clinical Infection Research, Hannover, Germany.
Citation:
ABHD5/CGI-58, the Chanarin-Dorfman Syndrome Protein, Mobilises Lipid Stores for Hepatitis C Virus Production. 2016, 12 (4):e1005568 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
Apr-2016
URI:
http://hdl.handle.net/10033/607736
DOI:
10.1371/journal.ppat.1005568
PubMed ID:
27124600
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the department experimental Virology([TC]EVIR)

Full metadata record

DC FieldValue Language
dc.contributor.authorVieyres, Gabrielleen
dc.contributor.authorWelsch, Kathrinen
dc.contributor.authorGerold, Gisaen
dc.contributor.authorGentzsch, Julianeen
dc.contributor.authorKahl, Sinaen
dc.contributor.authorVondran, Florian W Ren
dc.contributor.authorKaderali, Larsen
dc.contributor.authorPietschmann, Thomasen
dc.date.accessioned2016-05-03T13:15:16Zen
dc.date.available2016-05-03T13:15:16Zen
dc.date.issued2016-04en
dc.identifier.citationABHD5/CGI-58, the Chanarin-Dorfman Syndrome Protein, Mobilises Lipid Stores for Hepatitis C Virus Production. 2016, 12 (4):e1005568 PLoS Pathog.en
dc.identifier.issn1553-7374en
dc.identifier.pmid27124600en
dc.identifier.doi10.1371/journal.ppat.1005568en
dc.identifier.urihttp://hdl.handle.net/10033/607736en
dc.description.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.en
dc.language.isoenen
dc.titleABHD5/CGI-58, the Chanarin-Dorfman Syndrome Protein, Mobilises Lipid Stores for Hepatitis C Virus Production.en
dc.typeArticleen
dc.contributor.departmentTwincore Centre for Experimental and Clinical Infection Research, Hannover, Germany.en
dc.identifier.journalPLoS pathogensen

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