Sustained survival of human hepatocytes in mice: A model for in vivo infection with human hepatitis B and hepatitis delta viruses

Kazuo Ohashi, Patricia L. Marion, Hiroyuki Nakai, Leonard Meuse, John M. Cullen, Bruno B. Bordier, Ralph Schwali, Harry B. Greenberg, Jeffrey S. Glenn, Mark A. Kay

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

Persistence of hepatocytes transplanted into the same or related species has been established. The long-term engraftment of human hepatocytes into rodents would be useful for the study of human viral hepatitis, where it might allow the species, technical and size limitations of the current animal models to be overcome. Although transgenic mice expressing the hepatitis B virus (HBV) genome produce infectious virus in their serum, the viral life cycle is not complete, in that the early stages of viral binding and entry into hepatocytes and production of an episomal transcriptional DNA template do not occur. As for hepatitis delta virus (HDV), another cause of liver disease, no effective therapy exists to eradicate infection, and it remains resistant even to recent regimens that have considerably changed the treatment of HBV (ref. 13). Here, we demonstrate long-term engraftment of primary human hepatocytes transplanted in a matrix under the kidney capsule of mice with administration of an agonistic antibody against c-Met. These mice were susceptible to HBV infection and completion of the vital life cycle. In addition, we demonstrate super-infection of the HBV-infected mice with HDV. Our results describe a new xenotransplant model that allows study of multiple aspects of human hepatitis viral infections, and may enhance studies of human liver diseases.

Original languageEnglish (US)
Pages (from-to)327-331
Number of pages5
JournalNature Medicine
Volume6
Issue number3
DOIs
StatePublished - Mar 2000
Externally publishedYes

Fingerprint

Hepatitis Delta Virus
Hepatitis B
Viruses
Hepatitis B virus
Hepatocytes
Virus Diseases
Infection
Life Cycle Stages
Hepatitis, Viral, Human
Liver Diseases
Liver
Life cycle
Transgenic Mice
Hepatitis
Capsules
Rodentia
Animal Models
Genome
Kidney
Antibodies

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Sustained survival of human hepatocytes in mice : A model for in vivo infection with human hepatitis B and hepatitis delta viruses. / Ohashi, Kazuo; Marion, Patricia L.; Nakai, Hiroyuki; Meuse, Leonard; Cullen, John M.; Bordier, Bruno B.; Schwali, Ralph; Greenberg, Harry B.; Glenn, Jeffrey S.; Kay, Mark A.

In: Nature Medicine, Vol. 6, No. 3, 03.2000, p. 327-331.

Research output: Contribution to journalArticle

Ohashi, K, Marion, PL, Nakai, H, Meuse, L, Cullen, JM, Bordier, BB, Schwali, R, Greenberg, HB, Glenn, JS & Kay, MA 2000, 'Sustained survival of human hepatocytes in mice: A model for in vivo infection with human hepatitis B and hepatitis delta viruses', Nature Medicine, vol. 6, no. 3, pp. 327-331. https://doi.org/10.1038/73187
Ohashi, Kazuo ; Marion, Patricia L. ; Nakai, Hiroyuki ; Meuse, Leonard ; Cullen, John M. ; Bordier, Bruno B. ; Schwali, Ralph ; Greenberg, Harry B. ; Glenn, Jeffrey S. ; Kay, Mark A. / Sustained survival of human hepatocytes in mice : A model for in vivo infection with human hepatitis B and hepatitis delta viruses. In: Nature Medicine. 2000 ; Vol. 6, No. 3. pp. 327-331.
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