title: Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein.
abstract: 360 million people are chronically infected with the human hepatitis B virus (HBV) and are consequently prone to develop liver cirrhosis and hepatocellular carcinoma. As approved therapeutic regimens-which modulate patients' antiviral defenses or inhibit the viral reverse transcriptase-are generally noncurative, strategies interfering with other HBV replication steps are required. Expanding on our demonstration that acylated peptides derived from the large HBV envelope protein block virus entry in vitro, we show their applicability to prevent HBV or woolly monkey hepatitis B virus infection in vivo, using immunodeficient urokinase-type plasminogen activator (uPA) mice repopulated with primary human or Tupaia belangeri hepatocytes. Accumulation of the peptides in the liver, their extraordinary inhibitory potency and specific mode of action permit subcutaneous delivery at very low doses. Inhibition of hepadnavirus entry thus constitutes a therapeutic approach to prevent primary HBV infection, such as after liver transplantation, and might also restrain virus spread in chronically infected patients.
authors.affiliation: Department of Medicine, University of Hamburg, Eppendorf, D-20246 Hamburg, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Petersen
authors.forename: Maura
authors.initials: M
authors.lastname: Dandri
authors.forename: Walter
authors.initials: W
authors.lastname: Mier
authors.forename: Marc
authors.initials: M
authors.lastname: Lütgehetmann
authors.forename: Tassilo
authors.initials: T
authors.lastname: Volz
authors.forename: Fritz
authors.initials: F
authors.lastname: von Weizsäcker
authors.forename: Uwe
authors.initials: U
authors.lastname: Haberkorn
authors.forename: Lutz
authors.initials: L
authors.lastname: Fischer
authors.forename: Joerg-Matthias
authors.initials: JM
authors.lastname: Pollok
authors.forename: Berit
authors.initials: B
authors.lastname: Erbes
authors.forename: Stefan
authors.initials: S
authors.lastname: Seitz
authors.forename: Stephan
authors.initials: S
authors.lastname: Urban
mesh_terms: D000215:Acylation; D000595:Amino Acid Sequence; D000818:Animals; D053819:Atelinae / Q000821:virology; D004268:DNA-Binding Proteins / Q000235:genetics; D006509:Hepatitis B / Q000517:prevention & control* / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000737:chemistry; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000821:virology; D008297:Male; D051379:Mice; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014417:Tupaia; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D004268:DNA-Binding Proteins; D006514:Hepatitis B Surface Antigens; C096362:L protein, hepatitis B virus; C499308:Rag2 protein, mouse; D014759:Viral Envelope Proteins; D014568:Urokinase-Type Plasminogen Activator