Establishment of the Dual Humanized TK-NOG Mouse Model for HIV-associated Liver Pathogenesis

Raghubendra Singh Dagur, Weimin Wang, Edward Makarov, Yimin Sun, Larisa Y. Poluektova

Research output: Contribution to journalArticle

Abstract

Despite the increased life expectancy of patients infected with human immunodeficiency virus-1 (HIV-1), liver disease has emerged as a common cause of their morbidity. The liver immunopathology caused by HIV-1 remains elusive. Small xenograft animal models with human hepatocytes and human immune system can recapitulate the human biology of the disease's pathogenesis. Herein, a protocol is described to establish a dual humanized mouse model through human hepatocytes and CD34+ hematopoietic stem/progenitor cells (HSPCs) transplantation, to study liver immunopathology as observed in HIV-infected patients. To achieve dual reconstitution, male TK-NOG (NOD.Cg-Prkdcscid Il2rgtm1Sug Tg(Alb-TK)7-2/ShiJic) mice are intraperitoneally injected with ganciclovir (GCV) doses to eliminate mouse transgenic liver cells, and with treosulfan for nonmyeloablative conditioning, both of which facilitate human hepatocyte (HEP) engraftment and human immune system (HIS) development. Human albumin (ALB) levels are evaluated for liver engraftment, and the presence of human immune cells in blood detected by flow cytometry confirms the establishment of human immune system. The model developed using the protocol described here resembles multiple components of liver damage from HIV-1 infection. Its establishment could prove to be essential for studies of hepatitis virus co-infection and for the evaluation of antiviral and antiretroviral drugs.

Original languageEnglish (US)
JournalJournal of visualized experiments : JoVE
Issue number151
DOIs
StatePublished - Sep 11 2019

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Liver
HIV
Viruses
Immune system
treosulfan
HIV-1
Hepatocytes
Immune System
Virus Diseases
Ganciclovir
Flow cytometry
Stem cells
Heterografts
Antiviral Agents
Albumins
Hepatitis Viruses
Animals
Blood
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells

ASJC Scopus subject areas

  • Neuroscience(all)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Establishment of the Dual Humanized TK-NOG Mouse Model for HIV-associated Liver Pathogenesis. / Dagur, Raghubendra Singh; Wang, Weimin; Makarov, Edward; Sun, Yimin; Poluektova, Larisa Y.

In: Journal of visualized experiments : JoVE, No. 151, 11.09.2019.

Research output: Contribution to journalArticle

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