title: Entry of duck hepatitis B virus into primary duck liver and kidney cells after discovery of a fusogenic region within the large surface protein.
abstract: Hepatitis B viruses exhibit a narrow host range specificity that is believed to be mediated by a domain of the large surface protein, designated L. For duck hepatitis B virus, it has been shown that the pre-S domain of L binds to carboxypeptidase D, a cellular receptor present in many species on a wide variety of cell types. Nonetheless, only hepatocytes become infected. It has remained vague which viral features determine host range specificity and organotropicity. By using chymotrypsin to treat duck hepatitis B virus, we addressed the question of whether a putative fusogenic region within the amino-terminal end of the small surface protein may participate in viral entry and possibly constitute one of the determinants of the host range of the virus. Addition of the enzyme to virions resulted in increased infectivity. Remarkably, even remnants of enzyme-treated subviral particles proved to be inhibitory to infection. A noninfectious deletion mutant devoid of the binding region for carboxypeptidase D could be rendered infectious for primary duck hepatocytes by treatment with chymotrypsin. Although because of the protease treatment mutant and wild-type viruses may have become infectious in an unspecific and receptor-independent manner, their host range specificity was not affected, as shown by the inability of the virus to replicate in different hepatoma cell lines, as well as primary chicken hepatocytes. Instead, the organotropicity of the virus could be reduced, which was demonstrated by infection of primary duck kidney cells.
authors.affiliation: Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Martinistrasse 52, D-20251 Hamburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Maenz
authors.forename: Shau-Feng
authors.initials: SF
authors.lastname: Chang
authors.forename: Alicja
authors.initials: A
authors.lastname: Iwanski
authors.forename: Michael
authors.initials: M
authors.lastname: Bruns
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002645:Chickens; D002918:Chymotrypsin / Q000378:metabolism; D004372:Ducks; D015611:Hepatitis B Virus, Duck / Q000235:genetics / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology*; D007668:Kidney / Q000166:cytology / Q000821:virology*; D017434:Protein Structure, Tertiary; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology*; D014760:Viral Fusion Proteins / Q000235:genetics / Q000502:physiology*; D053586:Virus Internalization
chemical_list: C096362:L protein, hepatitis B virus; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D002918:Chymotrypsin