Modeling HIV-1 Mucosal Transmission and Prevention in Humanized Mice

Methods Mol Biol. 2016:1354:203-20. doi: 10.1007/978-1-4939-3046-3_14.

Abstract

The new generation humanized mice (hu-mice) that permit continuous de novo generation of human hematopoietic cells have led to novel strategies in studying HIV-1 pathogenesis, prevention and therapies. HIV-1 infection of hu-mice results in chronic viremia and CD4+ T cell loss, thus mimicking key aspects of the disease progression. In addition, the new generation hu-mice are permissive for HIV-1 sexual transmission by vaginal and rectal routes thus allowing in vivo efficacy testing of new anti-HIV-1 drugs for prevention. Two leading models are currently being used, namely the hu-HSC mice and the BLT mice. Here we describe the methodology for generating both hu-HSC and BLT mice and their use in the study of HIV-1 transmission and prevention of infection by topical and oral administration of anti-retroviral drugs. Practical aspects of the methodologies are emphasized.

Keywords: HIV infection in humanized mice; HIV mucosal transmission; HIV pre-exposure prophylaxis; HIV vaginal and rectal transmission; HIV-1 PrEP; HIV-1 animal models; Hu-HSC and BLT mice; Modeling HIV transmission and prevention; PK-PD in HIV-1 PrEP; Preparation of humanized mice.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-HIV Agents / pharmacokinetics
  • Anti-HIV Agents / therapeutic use*
  • CD4-Positive T-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / virology
  • Cell Separation / methods
  • Disease Models, Animal
  • HIV Infections / pathology
  • HIV Infections / prevention & control*
  • HIV Infections / transmission*
  • HIV-1 / drug effects
  • HIV-1 / physiology*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Liver Transplantation
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Mucous Membrane / pathology
  • Mucous Membrane / virology*
  • Thymus Gland / transplantation

Substances

  • Anti-HIV Agents