Humanized mouse model for HIV research

Humanized Mice: Revolutionizing HIV-1 Research and Prevention

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Soraya Malik in Health & Wellness August 2025 • 4 min read.

"Discover how these innovative models are accelerating the development of effective strategies against mucosal transmission"


HIV-1, a human-specific pathogen, has long posed a significant challenge for researchers aiming to understand its complex pathogenesis and develop effective prevention and treatment strategies. Traditional animal models have proven inadequate in replicating the intricacies of HIV-1 infection in humans, hindering progress in the field. However, the advent of humanized mice (hu-mice) has revolutionized HIV-1 research, providing a powerful platform for studying the virus and testing novel interventions.

Hu-mice, engineered to possess human cells and tissues, offer a unique opportunity to mimic HIV-1 infection and disease progression in a living organism. These models have undergone remarkable advancements in recent years, with new generations of hu-mice exhibiting enhanced human immune system reconstitution and permissivity to HIV-1 infection. This improved fidelity to human biology has transformed hu-mice into invaluable tools for investigating HIV-1 pathogenesis, evaluating preventive measures, and developing therapeutic interventions.

Among the various hu-mice models, two prominent types stand out: hu-HSC mice and BLT mice. Both models support HIV-1 infection and immune responses, but they differ in their construction and characteristics. The hu-HSC model involves engraftment of human CD34+ hematopoietic stem cells (HSCs), while the BLT model involves transplantation of human fetal thymic and liver tissues along with CD34+ HSCs. These models each offer distinct advantages for studying different aspects of HIV-1 infection and prevention.

Modeling HIV-1 Mucosal Transmission

Humanized mouse model for HIV research

The primary route of HIV-1 transmission is through sexual contact, specifically via the vaginal or rectal mucosa. Therefore, understanding the mechanisms of mucosal transmission and developing effective prevention strategies are crucial for curbing the spread of the virus. Hu-mice have emerged as powerful tools for modeling HIV-1 mucosal transmission, enabling researchers to study the dynamics of infection and evaluate the efficacy of interventions.

Recent studies have demonstrated that both hu-HSC and BLT mice can be infected with HIV-1 through vaginal and rectal mucosal routes, mirroring the natural route of transmission in humans. This breakthrough has paved the way for in vivo efficacy testing of new anti-HIV-1 drugs for prevention, particularly pre-exposure prophylaxis (PrEP) strategies. By administering PrEP drugs topically or orally to hu-mice and then challenging them with HIV-1, researchers can assess the ability of these drugs to prevent infection.

  • Hu-mice can be infected with HIV-1 via vaginal and rectal routes, mimicking natural transmission.
  • Oral and topical PrEP strategies have shown success in hu-mice models.
  • Researchers can evaluate new anti-HIV-1 compounds in the pipeline.
The ability to model HIV-1 mucosal transmission in hu-mice has also facilitated the investigation of factors that influence the risk of infection. For example, researchers have used these models to study the role of the vaginal and rectal microbiota in HIV-1 susceptibility, as well as the impact of inflammation and immune activation on transmission rates. This knowledge is critical for developing targeted prevention strategies that address specific risk factors and vulnerabilities.

The Future of HIV-1 Research

Humanized mice have revolutionized HIV-1 research by providing a physiologically relevant platform for studying the virus and evaluating new prevention and treatment strategies. Their ability to model HIV-1 mucosal transmission has opened new avenues for understanding the dynamics of infection and developing effective interventions. As hu-mice models continue to evolve and improve, they hold immense promise for accelerating progress towards ending the HIV/AIDS pandemic.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1007/978-1-4939-3046-3_14, Alternate LINK

Title: Modeling Hiv-1 Mucosal Transmission And Prevention In Humanized Mice

Journal: Methods in Molecular Biology

Publisher: Springer New York

Authors: Milena Veselinovic, Paige Charlins, Ramesh Akkina

Published: 2016-01-01

Everything You Need To Know

1

What are humanized mice (hu-mice) and why are they important in HIV-1 research?

Humanized mice, or hu-mice, are engineered to contain human cells and tissues, enabling researchers to study HIV-1 infection and disease progression in a living organism in a way that traditional animal models could not. These models have become increasingly sophisticated, with newer generations exhibiting enhanced human immune system reconstitution and susceptibility to HIV-1 infection.

2

What are the key differences between hu-HSC mice and BLT mice, and what advantages does each model offer for HIV-1 studies?

Hu-HSC mice are created by engrafting human CD34+ hematopoietic stem cells (HSCs) into mice. BLT mice, on the other hand, are generated through the transplantation of human fetal thymic and liver tissues along with CD34+ HSCs. Both models can support HIV-1 infection and immune responses, but they have different characteristics that make them useful for studying different aspects of HIV-1 infection and prevention.

3

How are humanized mice being used to model HIV-1 mucosal transmission, and why is this significant for prevention strategies?

Researchers use hu-mice to model HIV-1 mucosal transmission, which is the primary route of HIV-1 transmission in humans. By infecting hu-HSC and BLT mice with HIV-1 through vaginal and rectal mucosal routes, mirroring the natural route of transmission, they can study the dynamics of infection and evaluate the effectiveness of interventions, such as pre-exposure prophylaxis (PrEP).

4

Beyond drug testing, what other aspects of HIV-1 infection risk can be studied using humanized mice models?

The ability to model HIV-1 mucosal transmission in hu-mice allows researchers to investigate factors that influence the risk of infection, such as the role of the vaginal and rectal microbiota in HIV-1 susceptibility, and the impact of inflammation and immune activation on transmission rates. Understanding these factors is critical for developing targeted prevention strategies that address specific risk factors and vulnerabilities.

5

What is the overall impact of humanized mice on HIV-1 research, and what does the future hold for their role in combating the HIV/AIDS pandemic?

The use of hu-mice has revolutionized HIV-1 research and has opened new avenues for understanding the dynamics of infection and developing effective interventions. As hu-mice models continue to evolve and improve, they hold great promise for accelerating progress towards ending the HIV/AIDS pandemic. The future may involve more refined models that more accurately mimic the human immune system and transmission pathways, leading to even more effective prevention and treatment strategies.

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