title: Chronic infection with hepatitis B viruses and antiviral drug evaluation in uPA mice after liver repopulation with tupaia hepatocytes.
abstract: OBJECTIVE
  Transplantation of primary human hepatocytes and establishment of hepatitis B virus (HBV) infection in immunodeficient urokinase plasminogen activator (uPA) transgenic mice was shown. However, the availability of usable primary human hepatocytes is very limited. Therefore, alternative and more accessible sources of hepatocytes permissive for HBV infection are highly desirable. Here we investigated the potential of primary hepatocytes from the tree shrew Tupaia belangeri that were shown to be susceptible to HBV infection.
  
  
  METHODS
  Freshly isolated or cryopreserved primary tupaia hepatocytes were transplantated via intrasplenic injection into immunodeficient uPA/RAG-2 mice. Engrafted mice were then infected with HBV and woolly monkey (WM)-HBV positive sera.
  
  
  RESULTS
  Extensive proliferation of xenografted cells was demonstrated by the stable production of tupaia alpha1-antitrypsin in serum and liver of transplanted mice. Quantitative PCR assays demonstrated the presence of circulating viral particles as well as intracellular viral DNA, including covalently closed circular (ccc) DNA, in transplanted mice. Viral infection could be serially passaged in mice. Furthermore, viral replication was strongly inhibited by treating mice with adefovir dipivoxil.
  
  
  CONCLUSIONS
  uPA mice repopulated with tupaia hepatocytes represent a useful and more accessible model for HBV infection studies, including the evaluation of antiviral therapy and cccDNA.
authors.affiliation: Department of Medicine, University of Hamburg, Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Maura
authors.initials: M
authors.lastname: Dandri
authors.forename: Martin R
authors.initials: MR
authors.lastname: Burda
authors.forename: David M
authors.initials: DM
authors.lastname: Zuckerman
authors.forename: Karsten
authors.initials: K
authors.lastname: Wursthorn
authors.forename: Urte
authors.initials: U
authors.lastname: Matschl
authors.forename: Joerg M
authors.initials: JM
authors.lastname: Pollok
authors.forename: Xavier
authors.initials: X
authors.lastname: Rogiers
authors.forename: Andreas
authors.initials: A
authors.lastname: Gocht
authors.forename: Josef
authors.initials: J
authors.lastname: Köck
authors.forename: Hubert E
authors.initials: HE
authors.lastname: Blum
authors.forename: Fritz
authors.initials: F
authors.lastname: von Weizsäcker
authors.forename: Joerg
authors.initials: J
authors.lastname: Petersen
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D004270:DNA, Circular / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D004195:Disease Models, Animal; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000209:etiology* / Q000821:virology; D022781:Hepatocytes / Q000637:transplantation*; D051379:Mice; D063065:Organophosphonates / Q000627:therapeutic use; D014183:Transplantation, Heterologous; D014417:Tupaia; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000502:physiology*
chemical_list: D000998:Antiviral Agents; D004270:DNA, Circular; D004279:DNA, Viral; D063065:Organophosphonates; D014568:Urokinase-Type Plasminogen Activator; D000225:Adenine; C106812:adefovir dipivoxil