Humanized nog mice for intravaginal hiv exposure and treatment of hiv infection

Anna H.F. Andersen, Stine S.F. Nielsen, Rikke Olesen, Katharina Mack, Frederik Dagnæs-Hansen, Niels Uldbjerg, Lars Østergaard, Ole S. Søgaard, Paul W. Denton, Martin Tolstrup

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

Humanized mice provide a sophisticated platform to study human immunodeficiency virus (HIV) virology and to test antiviral drugs. This protocol describes the establishment of a human immune system in adult NOG mice. Here, we explain all the practical steps from isolation of umbilical cord blood derived human CD34+ cells and their subsequent intravenous transplantation into the mice, to the manipulation of the model through HIV infection, combination antiretroviral therapy (cART), and blood sampling. Approximately 75,000 hCD34+ cells are injected intravenously into the mice and the level of human chimerism, also known as humanization, in the peripheral blood is estimated longitudinally for months by flow cytometry. A total of 75,000 hCD34+ cells yields 20%–50% human CD45+ cells in the peripheral blood. The mice are susceptible to intravaginal infection with HIV and blood can be sampled once weekly for analysis, and twice monthly for extended periods. This protocol describes an assay for quantification of plasma viral load using droplet digital PCR (ddPCR). We show how the mice can be effectively treated with a standard-of-care cART regimen in the diet. The delivery of cART in the form of regular mouse chow is a significant refinement of the experimental model. This model can be used for preclinical analysis of both systemic and topical pre-exposure prophylaxis compounds as well as for testing of novel treatments and HIV cure strategies.

Original languageEnglish (US)
Article numbere60723
JournalJournal of Visualized Experiments
Volume2020
Issue number155
DOIs
StatePublished - Jan 2019

Keywords

  • CART
  • CCR5
  • DdPCR
  • HIV
  • Humanized mice
  • Immunology and Infection
  • Immunology and infection
  • Issue 155
  • NOG mouse
  • Stem cells

ASJC Scopus subject areas

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

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