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Updated: Mar 10, 2026
Lipid Droplet Isolation for Quantitative Mass Spectrometry Analysis
Published on: April 17, 2017
The lipid droplet-associated protein perilipin 3 facilitates hepatitis C virus-driven hepatic steatosis
Daniel Ferguson1,2, Jun Zhang2, Matthew A Davis2
1Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH.
Insights
Hepatitis C virus (HCV) core protein induces liver fat accumulation by interacting with perilipin 3 (PLIN3). Knocking down PLIN3 in mice reduced HCV-induced steatosis, highlighting PLIN3
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Background:
- Hepatitis C virus (HCV) infection affects 170 million globally, often leading to hepatic steatosis.
- HCV core protein alone can induce hepatic steatosis and associates with lipid droplets (LDs) for viral assembly.
- LDs are crucial for lipid storage and serve as platforms for HCV assembly, suggesting a key role in viral hepatitis pathogenesis.
Purpose of the Study:
- To investigate the role of the host LD scaffold protein, perilipin 3 (PLIN3), in HCV core protein-induced hepatic steatosis.
- To determine if PLIN3 is essential for the development of steatosis during HCV infection.
Main Methods:
- Studied HCV core-induced hepatic steatosis in transgenic mice.
- Utilized antisense oligonucleotide-mediated knockdown of PLIN3 in vivo.
- Assessed steatosis in mice fed either a standard chow or a moderate-fat diet.
Main Results:
- PLIN3 knockdown significantly blunted HCV core-induced hepatic steatosis.
- This effect was observed in mice on both chow and moderate-fat diets.
- Demonstrated that PLIN3 is essential for core-induced steatosis.
Conclusions:
- The LD scaffold protein, PLIN3, is essential for HCV core-induced hepatic steatosis.
- These findings provide new insights into the pathogenesis of HCV and the role of LDs.
Abstract:
Hepatitis C virus (HCV) is an enveloped RNA virus responsible for 170 million cases of viral hepatitis worldwide. Over 50% of chronically infected HCV patients develop hepatic steatosis, and steatosis can be induced by expression of HCV core protein (core) alone. Additionally, core must associate with cytoplasmic lipid droplets (LDs) for steatosis development and viral particle assembly. Due to the importance of the LD as a key component of hepatic lipid storage and as a platform for HCV particle assembly, it seems this dynamic subcellular organelle is a gatekeeper in the pathogenesis of viral hepatitis. Here, we hypothesized that core requires the host LD scaffold protein, perilipin (PLIN)3, to induce hepatic steatosis. To test our hypothesis in vivo, we have studied core-induced hepatic steatosis in the absence or presence of antisense oligonucleotide-mediated knockdown of PLIN3. PLIN3 knockdown blunted HCV core-induced steatosis in transgenic mice fed either chow or a moderate fat diet. Collectively, our studies demonstrate that the LD scaffold protein, PLIN3, is essential for HCV core-induced hepatic steatosis and provide new insights into the pathogenesis of HCV.
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