Hepatitis C virus p7 mediates membrane-to-membrane adhesion

Lee, Gi Young; Lee, Sora; Lee, Hye‐Ra; Yoo, Doo-Yeol

doi:10.1016/j.bbalip.2016.06.011

Cited by 4 publications

(11 citation statements)

References 35 publications

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“…We also tested the HCV p7 protein (a known cause of membrane permeabilization) as a positive control. 19,22 These results indicated that HBx directly induces membrane permeabilization, independently of other cellular proteins.…”

Section: Hbx Induces Membrane Permeabilizationmentioning

confidence: 79%

“…As HBx was shown to be inserted into the mitochondrial outer membrane via its transmembrane domain (residues 53-70), we generated liposomes with a rat liver mitochondrial outer membrane composition, as previously reported. 18,19 To observe the HBx localization in liposomes, we prepared mitochondrial outer membrane-mimic giant unilamellar vesicles (MOM-GUVs) including ATTO 390-DOPE. We treated the recombinant HBx protein for 2 minutes, and HBx-targeted MOM-GUVs were then stained with nickel-nitrilotriacetate conjugated to ATTO 488 fluorescent dye (NTA-ATTO 488) for the detection of poly-Histagged HBx by fluorescence microscopy.…”

Section: The Recombinant Hbx Protein Targets Mitochondrial Outer Mementioning

confidence: 99%

“…33,34 In the case of HCV p7, the protein forms hexameric complexes that act as ion channels permeable to cations to enhance the entry and escape of viral particles. 19,35,36 HBx also reduces the transmembrane potential and induces apoptosis by interacting with VDAC3. 20 HBx mainly has been studied in terms of its regulation of signalling cascades, including its interaction with several cellular proteins.…”

Section: The Influenza a Virus Pb1-f2 Protein Interacts With Vdac1 Anmentioning

confidence: 99%

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A direct role for hepatitis B virus X protein in inducing mitochondrial membrane permeabilization

Lee

Cho

et al. 2018

Journal of Viral Hepatitis

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Hepatitis B virus X protein (HBx) acts as a multifunctional protein that regulates intracellular signalling pathways during HBV infection. It has mainly been studied in terms of its interaction with cellular proteins. Here, we show that HBx induces membrane permeabilization independently of the mitochondrial permeability transition pore complex. We generated mitochondrial outer membrane-mimic liposomes to observe the direct effects of HBx on membranes. We found that HBx induced membrane permeabilization, and the region comprising the transmembrane domain and the mitochondrial-targeting sequence was sufficient for this process. Membrane permeabilization was inhibited by nonselective channel blockers or by N-(n-nonyl)deoxynojirimycin (NN-DNJ), a viroporin inhibitor. Moreover, NN-DNJ inhibited HBx-induced mitochondrial depolarization in Huh-7 cells. Based on the results of this study, we can postulate that the HBx protein itself is sufficient to induce mitochondrial membrane permeabilization. Our finding provides important information for a strategy of HBx targeting during HBV treatment.

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Section: Hbx Induces Membrane Permeabilizationmentioning

confidence: 79%

Section: The Recombinant Hbx Protein Targets Mitochondrial Outer Mementioning

confidence: 99%

Section: The Influenza a Virus Pb1-f2 Protein Interacts With Vdac1 Anmentioning

confidence: 99%

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A direct role for hepatitis B virus X protein in inducing mitochondrial membrane permeabilization

Lee

Cho

et al. 2018

Journal of Viral Hepatitis

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“…To investigate the lipid preference of HCV p7, we obtained a 5-carboxytetramethylrhodamine (TAMRA)-labeled p7 synthesized by solid-state peptide synthesis, as reported previously [12], and dissolved it in 50% trifluoroethanol (TFE), which is a solvent for hydrophobic alpha-helical proteins [14]. Natural phospholipids (PC, PE, PI, PS, phosphatidylglycerol (PG), phosphatidic acid (PA), and cardiolipin (CL)) were blotted on the supported nitrocellulose membrane, and a protein lipid overlay (PLO) assay was performed to examine the direct interaction of p7 with phospholipids.…”

Section: Hcv P7 Specifically Interacts With Psmentioning

confidence: 99%

“…In addition, it was recently suggested that the novel function of HCV p7 was to play a role in membrane adhesion in the budding process. Lee et al proposed that HCV p7 can interact with lipid rafts to cause lipid raft adhesion in artificial liposomal systems, and this function was independent of its pore-forming activity [12].…”

Section: Introductionmentioning

confidence: 99%

Hepatitis C Virus p7 Induces Membrane Permeabilization by Interacting with Phosphatidylserine

Lee

You

et al. 2020

IJMS

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Hepatitis C virus (HCV) p7 is known to be a nonselective cation channel for HCV maturation. Because the interaction of HCV proteins with host lipids in the endoplasmic reticulum membrane is crucial for the budding process, the identification of p7–lipid interactions could be important for understanding the HCV life cycle. Here, we report that p7 interacts with phosphatidylserine (PS) to induce membrane permeabilization. The interaction of p7 with PS was not inhibited by Gd3+ ions, which have been known to interact with negatively charged lipids, but channel activity and p7-induced mitochondrial depolarization were inhibited by Gd3+ ions. From the present results, we suggest that the p7–PS interaction plays an essential role in regulating its ion channel function and could be a potential molecular target for anti-HCV therapy.

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Ultrastructural and biochemical basis for hepatitis C virus morphogenesis

et al. 2017

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Chronic infection with HCV is a leading cause of cirrhosis, hepatocellular carcinoma and liver failure. One of the least understood steps in the HCV life cycle is the morphogenesis of new viral particles. HCV infection alters the lipid metabolism and generates a variety of microenvironments in the cell cytoplasm that protect viral proteins and RNA promoting viral replication and assembly. Lipid droplets (LDs) have been proposed to link viral RNA synthesis and virion assembly by physically associating these viral processes. HCV assembly, envelopment, and maturation have been shown to take place at specialized detergent-resistant membranes in the ER, rich in cholesterol and sphingolipids, supporting the synthesis of luminal LDs-containing ApoE. HCV assembly involves a regulated allocation of viral and host factors to viral assembly sites. Then, virus budding takes place through encapsidation of the HCV genome and viral envelopment in the ER. Interaction of ApoE with envelope proteins supports the viral particle acquisition of lipids and maturation. HCV secretion has been suggested to entail the ion channel activity of viral p7, several components of the classical trafficking and autophagy pathways, ESCRT, and exosome-mediated export of viral RNA. Here, we review the most recent advances in virus morphogenesis and the interplay between viral and host factors required for the formation of HCV virions.

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Hepatitis C virus p7 mediates membrane-to-membrane adhesion

Cited by 4 publications

References 35 publications

A direct role for hepatitis B virus X protein in inducing mitochondrial membrane permeabilization

A direct role for hepatitis B virus X protein in inducing mitochondrial membrane permeabilization

Hepatitis C Virus p7 Induces Membrane Permeabilization by Interacting with Phosphatidylserine

Ultrastructural and biochemical basis for hepatitis C virus morphogenesis

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