Mukesh Kumar1, Sriram Bandi, Kang Cheng, Sanjeev Gupta. 1. Marion Bessin Liver Research Center, Cancer Research Center, Diabetes Research Center, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA.
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. AIMS: 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.
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 micehepatitis 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. AIMS: 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/SCIDmice. 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/SCIDmice. 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: A A Demetriou; J F Whiting; D Feldman; S M Levenson; N R Chowdhury; A D Moscioni; M Kram; J R Chowdhury Journal: Science Date: 1986-09-12 Impact factor: 47.728
Authors: M Dandri; M R Burda; E Török; J M Pollok; A Iwanska; G Sommer; X Rogiers; C E Rogler; S Gupta; H Will; H Greten; J Petersen Journal: Hepatology Date: 2001-04 Impact factor: 17.425
Authors: S Saporta; C Borlongan; J Moore; E Mejia-Millan; S L Jones; P Bonness; T S Randall; R C Allen; T B Freeman; P R Sanberg Journal: Cell Transplant Date: 1997 Nov-Dec Impact factor: 4.139