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Updated: Aug 5, 2025
Phagosome Migration and Velocity Measured in Live Primary Human Macrophages Infected with HIV-1
Published on: September 5, 2016
Productive HIV-1 infection of tissue macrophages by fusion with infected CD4+ T cells
Rémi Mascarau1,2, Marie Woottum3, Léa Fromont1
1Institut de Pharmacologie et Biologie Structurale (IPBS), Université de Toulouse, Centre National de la Recherche Scientifique, Université Toulouse III - Paul Sabatier (UPS) , Toulouse, France.
Abstract:
Macrophages are essential for HIV-1 pathogenesis and represent major viral reservoirs. Therefore, it is critical to understand macrophage infection, especially in tissue macrophages, which are widely infected in vivo, but poorly permissive to cell-free infection. Although cell-to-cell transmission of HIV-1 is a determinant mode of macrophage infection in vivo, how HIV-1 transfers toward macrophages remains elusive. Here, we demonstrate that fusion of infected CD4+ T lymphocytes with human macrophages leads to their efficient and productive infection. Importantly, several tissue macrophage populations undergo this heterotypic cell fusion, including synovial, placental, lung alveolar, and tonsil macrophages. We also find that this mode of infection is modulated by the macrophage polarization state. This fusion process engages a specific short-lived adhesion structure and is controlled by the CD81 tetraspanin, which activates RhoA/ROCK-dependent actomyosin contractility in macrophages. Our study provides important insights into the mechanisms underlying infection of tissue-resident macrophages, and establishment of persistent cellular reservoirs in patients.
Insights
Human immunodeficiency virus type 1 (HIV-1) infects tissue macrophages through fusion with infected CD4+ T cells. This cell-to-cell transmission is crucial for establishing persistent viral reservoirs in patients.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Macrophages are critical for human immunodeficiency virus type 1 (HIV-1) pathogenesis and serve as major viral reservoirs.
- Tissue macrophages are widely infected in vivo but are poorly susceptible to cell-free HIV-1 infection, necessitating investigation into alternative transmission routes.
Purpose of the Study:
- To elucidate the mechanism by which HIV-1 infects tissue macrophages.
- To identify the cellular players and molecular pathways involved in HIV-1 transfer to macrophages.
Main Methods:
- Investigated heterotypic cell fusion between HIV-1-infected CD4+ T lymphocytes and various human tissue macrophage populations.
- Analyzed the role of macrophage polarization state in HIV-1 infection.
- Examined the involvement of CD81 tetraspanin and RhoA/ROCK signaling in the fusion process.
Main Results:
- Fusion of infected CD4+ T lymphocytes with human macrophages results in efficient and productive HIV-1 infection.
- Synovial, placental, lung alveolar, and tonsil macrophages are susceptible to this fusion-mediated infection.
- Macrophage polarization state influences the efficiency of this infection mode.
- CD81 tetraspanin regulates the fusion process via RhoA/ROCK-dependent actomyosin contractility.
Conclusions:
- Cell-to-cell fusion represents a significant pathway for HIV-1 infection of tissue-resident macrophages.
- Understanding this mechanism provides insights into the establishment of persistent HIV-1 reservoirs in patients.
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