Targeting the hepatitis B virus precore antigen with a novel IgNAR single variable domain intrabody
Autor: | Katherine Merne Griffiths, Sally Soppe, Olan Dolezal, Renae Walsh, Peter Revill, Danni Colledge, Liza Cabuang, Angeline Bartholomeusz, Stewart D. Nuttall, Stephen Locarnini |
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Rok vydání: | 2011 |
Předmět: |
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 |
Zdroj: | Virology. 411:132-141 |
ISSN: | 0042-6822 |
Popis: | 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. |
Databáze: | OpenAIRE |
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