A novel system for efficient gene transfer into primary human hepatocytes via cell‐permeable hepatitis B virus–like particle†

Brandenburg, Boerries; Stöckl, Lars; Gutzeit, Cindy; Roos, Martin; Lupberger, Joachim; Schwartlander, Ruth; Gelderblom, Hans R.; Sauer, Igor M.; Hofschneider, Peter Hans; Hildt, Eberhard

doi:10.1002/hep.20950

Cited by 36 publications

(44 citation statements)

References 46 publications

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“…To discriminate these cells from cells producing infectious viral particles, Huh9-13 cells were designated subgenomic repliconexpressing cells. Isolation, cultivation, and infection of primary human hepatocytes (PHHs) were performed as described previously (27,28). The use of primary human hepatocytes was approved by the ethics committee of the Medical Faculty of the University of Frankfurt (decision 343/13).…”

Section: Methodsmentioning

confidence: 99%

The Autophagosomal SNARE Protein Syntaxin 17 Is an Essential Factor for the Hepatitis C Virus Life Cycle

Ren

Elgner

Jiang

et al. 2016

J Virol

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1Seventy million people worldwide are chronically infected with hepatitis C virus (HCV). Chronic HCV infection is associated with an elevated risk of developing liver cirrhosis and hepatocellular carcinoma (1). HCV is a single-stranded, positivesense RNA virus that belongs to the Flaviviridae family. The viral RNA encodes a single polyprotein of about 3,100 amino acids, which is cleaved co-and posttranslationally by cellular and viral proteases into 10 viral proteins: the structural proteins (core, E1, E2), which build up the viral particles; the p7 polypeptide, which forms an ion channel; and the nonstructural (NS) proteins (NS2, NS3, NS4A, NS4B, NS5A, and NS5B), which support viral replication and assembly processes (2-5).NS5A is known to act as a regulator of intracellular signal transduction cascades. The kinase c-Raf was identified to bind to the C-terminal domain of NS5A. Thereby, c-Raf is located at the HCV replication complex (6, 7). The interaction of NS5A with c-Raf leads to the activation of c-Raf in association with the phosphorylation of c-Raf at serine 338 (6, 7). Moreover, it was found that inhibition of c-Raf blocks HCV replication (6,8). However, due to the delocalization of c-Raf to the replicon complex/endoplasmic reticulum (ER) membrane, c-Raf in HCV-replicating cells is withdrawn from the classic MEK/extracellular signal-regulated kinase (ERK) signaling pathway (6). Therefore, although c-Raf is activated in HCV-replicating cells, signal transduction to the MEK/ERK pathway is impaired.The HCV infection cycle is tightly associated with lipid metabolism. HCV replication occurs on the cytoplasmic face of the ER in the replication complexes (RCs) formed by nonstructural proteins. HCV replication and morphogenesis take place at specialized rearranged intracellular ER membranes, the socalled membranous web, that are enriched in proteins involved

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Section: Methodsmentioning

confidence: 99%

The Autophagosomal SNARE Protein Syntaxin 17 Is an Essential Factor for the Hepatitis C Virus Life Cycle

Ren

Elgner

Jiang

et al. 2016

J Virol

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“…Indirect Immunofluorescence Analysis-Fixation and staining were performed as described recently (39). Immunofluorescence staining was analyzed using a confocal laser scanning microscope (CLSM 510 Carl Zeiss, Germany).…”

Section: Sds-page and Western Blot Analysis-sds-pagementioning

confidence: 99%

Hepatitis B Virus Induces Expression of Antioxidant Response Element-regulated Genes by Activation of Nrf2

Schaedler

Krause

Himmelsbach

et al. 2010

Journal of Biological Chemistry

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“…To date, several studies have been performed aimed at developing HBc-based chimeric VLPs that could serve as potential nanovehicles to target various cells. 16,34,35 In this study, we tested the possibility of exploiting the B. burgdorferi FN-binding protein BBK32 for modification of HBc particles to create an FN-targeting system with subsequent transduction of target cells.…”

Section: Discussionmentioning

confidence: 99%

Fibronectin-binding nanoparticles for intracellular targeting addressed by B. burgdorferi BBK32 protein fragments

Ranka¹,

Petrovskis²,

Sominskaya³

et al. 2013

Nanomedicine: Nanotechnology, Biology and Medicine

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Virus-like particles (VLPs) are created by the self-assembly of multiple copies of envelope and/or capsid proteins from many viruses, mimicking the conformation of a native virus. Such noninfectious nanostructures are mainly used as antigen-presenting platforms, especially in vaccine research; however, some of them recently were used as scaffolds in biotechnology to produce targeted nanoparticles for intracellular delivery. This study demonstrates the creation of fusion VLPs using hepatitis B core protein-based system maintaining a fibronectin-binding property from B. burgdorferi BBK32 protein, including the evidence of particles' transmission to BHK-21 target cells via caveolae/rafts endocythosis. These results make this construct to be an attractive model in development of HBc-based nanoparticles for cellular targeting applications and highlights the fragment of B. burgdorferi BBK32 as a novel cellular uptake-promoting peptide.From the Clinical Editor: This paper discusses the nanotechnology-based application of self-assembling viral-like peptides (VLP-s) for targeted delivery using a hepatitis B core protein based system. Creating fusion VLPs may be an attractive model for cellular targeting applications. © 2013 Elsevier Inc. All rights reserved.Key words: Fibronectin; Nanoparticles; B. burgdorferi Various strategies in the design of nanoparticles (NPs) -particles in the size range 1 -1000 nm -aim to create new generations of drug-delivery vehicles, contrast agents, and diagnostic devices. 1 One of the relevant potentials of the nanomedicines is their intracellular targeting possibility. Effective intracellular drug delivery is important for therapeutic agents that have specific molecular targets inside a cell as well as for drugs that undergo extensive efflux from the cell by the efflux transporters. Thus, the ability to penetrate inside cells bypassing lysosomal degradation is one of the key problems in the rational design of pharmaceutical nanocarriers. 2 For this purpose, the surface of nanocarriers could be modified by certain internalizable ligands (e.g., folate, transferrin) or by cellpenetrating peptides, such as a trans-activating transcriptional activator (TaT), an integrin-binding peptide (RGD peptide) or polyArginine. 3 This approach is receiving increasing attention over the last years because it is efficient for a range of cell types, and various endocytotic mechanisms can be engaged to facilitate the internalization of a carrier. 2 Virus-like particles (VLPs) is a broad group of nanocarrier systems that exhibit great potential in biomedicine research, including targeted drug delivery. 4 VLPs are self-assembling noninfectious supramolecular structures that have been produced from structural proteins of a wide variety of virus families. The unique features of VLPs are proper dimensions for nanoscale applications, size homogeneity, a large surface area-to-mass ratio, a symmetric macromolecular organization, biodegradability, biocompatibility and ease of production/ purification. 5 In addit...

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A novel system for efficient gene transfer into primary human hepatocytes via cell‐permeable hepatitis B virus–like particle†

Cited by 36 publications

References 46 publications

The Autophagosomal SNARE Protein Syntaxin 17 Is an Essential Factor for the Hepatitis C Virus Life Cycle

The Autophagosomal SNARE Protein Syntaxin 17 Is an Essential Factor for the Hepatitis C Virus Life Cycle

Hepatitis B Virus Induces Expression of Antioxidant Response Element-regulated Genes by Activation of Nrf2

Fibronectin-binding nanoparticles for intracellular targeting addressed by B. burgdorferi BBK32 protein fragments

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