ArticleJournal of lipid research2013
Hepatitis C virus NS4B targets lipid droplets through hydrophobic residues in the amphipathic helices.
Article in Journal of lipid research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Lipid Droplets: Formation, Degradation, and Their Role in Cellular Responses to Flavivirus Infections.Microorganisms · 2024Review
- Comparative Analysis of Hepatitis C Virus NS5A Dynamics and Localization in Assembly-Deficient Mutants.Pathogens (Basel, Switzerland) · 2021Article
- A global lipid map defines a network essential for Zika virus replication.Nature communications · 2020Article
- HCV Pit Stop at the Lipid Droplet: Refuel Lipids and Put on a Lipoprotein Coat before Exit.Cells · 2019Review
- Suppression of Hepatitis C Virus Genome Replication and Particle Production by a Novel Diacylglycerol Acyltransferases Inhibitor.Molecules (Basel, Switzerland) · 2018Article
- Evolutionary Analysis Provides Insight Into the Origin and Adaptation of HCV.Frontiers in microbiology · 2018Article
- Opportunistic intruders: how viruses orchestrate ER functions to infect cells.Nature reviews. Microbiology · 2016Review
- Pathophysiology of lipid droplet proteins in liver diseases.Experimental cell research · 2016Review
- Exposure to dietary lipid leads to rapid production of cytosolic lipid droplets near the brush border membrane.Nutrition & metabolism · 2016Article
- Preclinical Characterization and In Vivo Efficacy of GSK8853, a Small-Molecule Inhibitor of the Hepatitis C Virus NS4B Protein.Antimicrobial agents and chemotherapy · 2015Article
- Lipid dysregulation in hepatitis C virus, and impact of statin therapy upon clinical outcomes.World journal of gastroenterology · 2015Review
- Hepatitis C virus entry is impaired by claudin-1 downregulation in diacylglycerol acyltransferase-1-deficient cells.Journal of virology · 2014Article
- Forkhead box transcription factor regulation and lipid accumulation by hepatitis C virus.Journal of virology · 2014Article
- Association of lipid droplet and hepatitis C virus proteins: insights for virus replication.Journal of lipid research · 2013Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipid droplets (LD) are dynamic storage organelles that are involved in lipid homeostasis. Hepatitis C virus (HCV) is closely associated with LDs. HCV Core and nonstructural (NS) proteins colocalize with LDs and presumably are involved in virion formation at that site. We demonstrated that HCV NS4B, an integral membrane protein in endoplasmic reticulum (ER), strongly targeted LDs. Confocal imaging studies showed that NS4B localized at the margins of LDs. Biochemical fractionation of HCV-replicating cells suggested that NS4B existed in membranes associated with LDs rather than on the LD surface membrane itself. The N- and C-terminal cytosolic domains of NS4B showed targeting of LDs, with the former being much stronger. In both domains, activity was present in the region containing an amphipathic α-helix, in which 10 hydrophobic residues were identified as putative determinants for targeting LDs. JFH1 mutants with alanine substitutions for the hydrophobic residues were defective for virus replication. W43A mutant with a single alanine substitution showed loss of association of NS4B with LDs and severely reduced release of infectious virions compared with wild-type JFH1. NS4B plays a crucial role in virus replication at the site of virion formation, namely, the microenvironment associated with LDs.
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