# A humanized mouse model for vaginal HIV-1 transmission.

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2021 · $236,250

## Abstract

Abstract
Animal models such as small non-human primates and humanized immune system mice
(humanized mice) are valuable tools to study HIV prevention by antiretroviral drugs or vaccines.
The human bone marrow-liver-thymus (BLT) mouse model allows reconstitution of human
lymphoid cells in gut and female reproductive tract (FRT), which makes humanized BLT mice
suitable for the studies of HIV mucosal transmission and pre-exposure prophylaxis. To generate
humanized BLT mice, human fetal liver and thymus tissue are implanted under the kidney capsule
of aforementioned immunodeficient mice engrafted with autologous human HSPCs. The major
limitations of the BLT model are: 1) it requires fetal derived human cells and tissues; 2) it develops
graft-versus-host disease. Therefore, it is important to develop humanized mouse models that
utilize non-fetal derived human HSPCs to reconstitute mucosal human immune system and are
susceptible to mucosal HIV transmission. We have developed humanized mouse models that
reconstituted human lymphocytes and myeloid cells in the female reproductive tract (FRT), which
allowed robust HIV-1 infection through vaginal exposure. Using this mouse model, we propose to
investigate: 1) Propagation and dissemination of infection after vaginal exposure to HIV-1; 2)
mucosal viral reservoirs in mice treated with antiretroviral drugs; 3) Viral-specific CD8+ T cells in
the FRT of HIV-infected mice. Our proposed study will develop a non-fetal derived humanized
mouse model that allows robust reconstitution of mucosal human immune cells in the FRT to
support vaginal HIV-1 transmission. In addition, it will help us gain a better insight into the human
immune responses in the FRT, which will provide implications to the T-cell based vaccine
development.

## Key facts

- **NIH application ID:** 10257652
- **Project number:** 1R21AI162262-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** LIANG SHAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $236,250
- **Award type:** 1
- **Project period:** 2021-08-20 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10257652

## Citation

> US National Institutes of Health, RePORTER application 10257652, A humanized mouse model for vaginal HIV-1 transmission. (1R21AI162262-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10257652. Licensed CC0.

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