HIV-1 cellular and tissue replication patterns in infected humanized mice

Area of Science:

• Immunology
• Virology
• Pathobiology

Background:

• Humanized mice are valuable models for studying HIV-1 (Human Immunodeficiency Virus type 1) pathobiology, offering insights into natural human disease processes.
• Understanding the tissue and cellular sites of HIV-1 infection is critical for accurately modeling human disease in these systems.

Purpose of the Study:

• To investigate the specific tissue and cellular locations of HIV-1 infection within humanized mice.
• To characterize the distribution and viral life cycle of HIV-1 in various cell subsets across multiple organs.

Main Methods:

• Analysis of HIV-1 infected human CD34+ hematopoietic stem cell engrafted mice.
• Flow cytometry and cell sorting to isolate specific cell populations, including progenitor cells and monocyte-macrophages.
• Detection of HIV-1 DNA and RNA in sorted cell subsets from bone marrow, blood, spleen, liver, gut, brain, kidney, and lungs.

Main Results:

• HIV-1 infection sites and viral life cycle dynamics varied significantly depending on the tissue compartment and infection time.
• Specific cell subsets, including CD34+ lineage negative progenitor cells and CD14+CD16+ monocyte-macrophages, harbored HIV-1 total and integrated DNA.
• Divergent proportions of multi-spliced and unspliced HIV-1 RNA were detected in different cell subsets, indicating active viral replication.

Conclusions:

• Humanized mice provide a viable platform for studying HIV-1 replication at multifaceted sites, including progenitor cells and monocyte-macrophages.
• These findings enhance the utility of humanized mice as an alternative to non-human primate models for HIV/AIDS research.
• The study contributes to a deeper understanding of HIV-1 pathogenesis and therapeutic development in a human-relevant context.