Premium
Llama‐derived single‐domain intrabodies inhibit secretion of hepatitis B virions in mice
Author(s) -
Serruys Benedikte,
Van Houtte Freya,
Verbrugghe Phebe,
LerouxRoels Geert,
Vanlandschoot Peter
Publication year - 2009
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.22609
Subject(s) - hbsag , hepatocellular carcinoma , hepatitis b virus , virology , secretion , endoplasmic reticulum , cirrhosis , antibody , in vivo , hepatitis b , antigen , biology , medicine , virus , immunology , cancer research , microbiology and biotechnology
Hepatitis B virus (HBV) infections cause 500,000 to 700,000 deaths per year as a consequence of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Efficient and safe antivirals to treat chronically infected patients and consequently to prevent development of hepatocellular carcinoma are still awaited. We isolated five single‐domain antibodies (VHHs) that recognize the most abundant envelope protein (S) of HBV. VHHs, when expressed and retained in the endoplasmic reticulum as intrabodies, reduced levels of secreted hepatitis B surface antigen (HBsAg) particles in a cellular HBV model. In a hydrodynamics‐based HBV mouse model, these intrabodies caused a marked reduction in HBsAg concentrations and a 10‐ to >100‐fold reduction in the concentration of HBV virions in plasma. Conclusion: VHHs potently inhibited secretion of HBV virions in vivo , showing that this approach might be useful in the treatment of HBV. To our knowledge, this is the first report of intrabody‐mediated inhibition of viral secretion in mammals. (H EPATOLOGY 2009;49:39‐49.)