title: Transplantation of human cells in the peritoneal cavity of immunodeficient mice for rapid assays of hepatitis B virus replication.
abstract: BACKGROUND
  Studies of natural hepatitis B virus infection must be restricted to humans or primates due to viral species-specificity. Alternative hepadnavirus animal models, e.g., woodchuck hepatitis virus in captive woodchucks, are not convenient, while in transgenic mice hepatitis B virus or viral proteins are expressed permanently through integrated genomes. Availability of small animal models that are easily produced and permit rapid assays will be quite helpful.
  
  
  OBJECTIVE
  We examined whether transplantation of human cells in the peritoneal cavity of mice will generate an appropriate mass of cells with hepatitis B virus replication.
  
  
  METHODS
  HepG2 2.2.15 cells were transplanted intraperitoneally into NOD/SCID mice. Replication of hepatitis B virus and viral gene expression was determined by analysis of blood and transplanted tissues with viral DNA and hepatitis B core antigen expression. Interruption of viral replication was examined.
  
  
  RESULTS
  After intraperitoneal transplantation with microcarrier scaffolds, 2.2.15 cells engrafted and proliferated in the peritoneal cavity of NOD/SCID mice. Hepatitis B virus replicated in transplanted 2.2.15 cells as shown by hepatitis B core antigen expression. Moreover, viral particles were secreted into the blood. Hepatitis B virus replication was susceptible to conventional antiviral drug therapy, such as lamivudine, as well as experimental antiviral gene therapy with a synthetic mimic of an antiviral cellular microRNA.
  
  
  CONCLUSIONS
  Intraperitoneal transplantation of human cells rapidly provided reservoirs of hepatitis B virus in mice. This simple xenotransplantation approach will be effective and convenient for studies of hepatitis B and other human viruses in vivo.
authors.affiliation: Marion Bessin Liver Research Center, Cancer Research Center, Diabetes Research Center, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Kumar
authors.forename: Sriram
authors.initials: S
authors.lastname: Bandi
authors.forename: Kang
authors.initials: K
authors.lastname: Cheng
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000818:Animals; D017690:Cell Transplantation; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010529:Peritoneal Cavity / Q000166:cytology*; D014183:Transplantation, Heterologous; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens