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PLoS One. 2016 Jun 9;11(6):e0156996. doi: 10.1371/journal.pone.0156996. eCollection 2016.

Distinct Roles for Intracellular and Extracellular Lipids in Hepatitis C Virus Infection.

Author information

1
Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, United States of America.
2
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, United States of America.
3
Department of Pharmacology, University of Virginia, Charlottesville, United States of America.
4
Department of Biology, University of Richmond, Richmond, United States of America.
5
Cropsolution Inc., Morrisville, United States of America.
6
Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, United States of America.

Abstract

Hepatitis C is a chronic liver disease that contributes to progressive metabolic dysfunction. Infection of hepatocytes by hepatitis C virus (HCV) results in reprogramming of hepatic and serum lipids. However, the specific contribution of these distinct pools of lipids to HCV infection remains ill defined. In this study, we investigated the role of hepatic lipogenesis in HCV infection by targeting the rate-limiting step in this pathway, which is catalyzed by the acetyl-CoA carboxylase (ACC) enzymes. Using two structurally unrelated ACC inhibitors, we determined that blockade of lipogenesis resulted in reduced viral replication, assembly, and release. Supplementing exogenous lipids to cells treated with ACC inhibitors rescued HCV assembly with no effect on viral replication and release. Intriguingly, loss of viral RNA was not recapitulated at the protein level and addition of 2-bromopalmitate, a competitive inhibitor of protein palmitoylation, mirrored the effects of ACC inhibitors on reduced viral RNA without a concurrent loss in protein expression. These correlative results suggest that newly synthesized lipids may have a role in protein palmitoylation during HCV infection.

PMID:
27280294
PMCID:
PMC4900644
DOI:
10.1371/journal.pone.0156996
[Indexed for MEDLINE]
Free PMC Article

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