iPS cell-derived model to study the interaction between tissue macrophage and HIV-1.
Youssef M Eltalkhawy1, Naofumi Takahashi1, Yasuo Ariumi1
1Joint Research Center for Human Retrovirus Infection, Kumamoto University, Honjo 2-2-1, Kumamoto-city, Kumamoto 860-0811, Japan.
Journal of Leukocyte Biology
|March 28, 2023
Summary
Researchers developed a new self-renewing macrophage model using induced pluripotent stem cells. This model effectively mimics HIV-1 interactions in tissue macrophages, offering new insights beyond traditional monocyte-derived models for HIV-1 persistence research.
Area of Science:
- Immunology
- Virology
- Stem Cell Biology
Background:
- Human Immunodeficiency Virus type 1 (HIV-1) persistence in macrophages hinders curative strategies.
- Current macrophage models, like monocyte-derived macrophages, do not fully represent tissue-resident macrophages, which originate from embryonic precursors and possess self-renewal capacity.
Purpose of the Study:
- To establish and validate a novel self-renewing macrophage model using human induced pluripotent stem cell-derived immortalized macrophage-like cells.
- To investigate the utility of this new model in studying HIV-1 replication and persistence, particularly in comparison to monocyte-derived macrophages.
Main Methods:
- Generation of immortalized macrophage-like cells from human induced pluripotent stem cells.
- Culture and differentiation of cells, cytokine-dependent proliferation assays.
- Assessment of macrophage functions, HIV-1 replication assays, and analysis of viral genetic material.
- Comparison of cellular phenotypes and viral dynamics with monocyte-derived macrophages.
Main Results:
- Induced pluripotent stem cell-derived immortalized macrophage-like cells demonstrated cytokine-dependent proliferation and retained key macrophage functions.
- These cells supported HIV-1 replication and exhibited phenotypes similar to infected monocyte-derived macrophages, including enhanced cell motility and resistance to viral cytopathic effects.
- Differences observed, such as faster enrichment of proviruses with deletions and enhanced inhibition of viral transcription, were linked to the proliferative capacity of the new model.
Conclusions:
- Human induced pluripotent stem cell-derived immortalized macrophage-like cells provide a valuable model for studying self-renewing tissue macrophages.
- This model offers a more accurate representation of HIV-1 interplay with tissue-resident macrophages than monocyte-derived macrophages alone.
- The model facilitates research into HIV-1 persistence mechanisms within self-renewing macrophage populations, crucial for developing effective cure strategies.
