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Targeting the hepatitis B virus precore antigen with a novel IgNAR single variable domain intrabody
- Source :
- Virology. 411:132-141
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- The Hepatitis B virus precore protein is processed in the endoplasmic reticulum (ER) into secreted hepatitis B e antigen (HBeAg), which acts as an immune tolerogen to establish chronic infection. Downregulation of secreted HBeAg should improve clinical outcome, as patients who effectively respond to current treatments (IFN-α) have significantly lower serum HBeAg levels. Here, we describe a novel reagent, a single variable domain (V(NAR)) of the shark immunoglobulin new antigen receptor (IgNAR) antibodies. V(NAR)s possess advantages in stability, size (~14 kDa) and cryptic epitope recognition compared to conventional antibodies. The V(NAR) domain displayed biologically useful affinity for recombinant and native HBeAg, and recognised a unique conformational epitope. To assess therapeutic potential in targeting intracellular precore protein to reduce secreted HBeAg, the V(NAR) was engineered for ER-targeted in vitro delivery to function as an intracellular antibody (intrabody). In vitro data from HBV/precore hepatocyte cell lines demonstrated effective intrabody regulation of precore/HBeAg.
- Subjects :
- Hepatitis B virus
Molecular Sequence Data
Endoplasmic Reticulum
medicine.disease_cause
Chronic hepatitis B
New antigen receptor
Intrabody
Epitope
Cell Line
Antigen
Virology
medicine
Humans
Hepatitis B e Antigens
Hepatitis B Antibodies
BIAcore kinetics
Hepatitis B e antigen
Biological Products
biology
virus diseases
Sequence Analysis, DNA
Molecular biology
digestive system diseases
Protein Transport
Precore
HBeAg
Hepatocytes
biology.protein
Bacteriophage display
Antibody
Single-Chain Antibodies
Conformational epitope
Subjects
Details
- ISSN :
- 00426822
- Volume :
- 411
- Database :
- OpenAIRE
- Journal :
- Virology
- Accession number :
- edsair.doi.dedup.....861d6811fa3f0203096255f3ad97ee51