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Updated: Sep 19, 2025
Phagosome Migration and Velocity Measured in Live Primary Human Macrophages Infected with HIV-1
Published on: September 5, 2016
Macropinosomes are a site of HIV-1 entry into primary CD4+ T cells
Tomoyuki Murakami1, Ricardo de Souza Cardoso1, Praveen Manivannan1
1Department of Microbiology & Immunology, University of Michigan Medical School, Ann Arbor, MI 48109.
Abstract:
HIV-1 has been observed to enter target cells at both the plasma membrane and endosomes. However, which pathways mediate its entry into primary CD4+ T cells, the major targets of this virus, remains unclear. Here, we show that HIV-1 can enter primary CD4+ T cells through macropinocytosis, a form of endocytosis. We found that HIV-1 can enter primary CD4+ T cells at both the plasma membrane and internal compartments, while entry into common T cell lines occurred primarily at the plasma membrane. Inhibition of macropinocytosis suppressed HIV-1 internalization into and subsequent fusion with primary CD4+ T cells regardless of the viral coreceptor usage. Microscopic analysis of viral contents exposed to the cytosol confirmed that HIV-1 fusion occurs at the macropinosomal membrane. Finally, the inhibition of macropinocytosis blocked HIV-1 infection of primary CD4+ T cells. Altogether, this study identifies macropinocytosis as one pathway for HIV-1 entry into primary CD4+ T cells.
Insights
Human immunodeficiency virus type 1 (HIV-1) enters crucial CD4+ T cells via macropinocytosis, a cellular uptake process. Inhibiting this pathway blocks viral entry and infection, revealing a key mechanism of HIV-1 cell entry.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Human immunodeficiency virus type 1 (HIV-1) infects CD4+ T cells, the primary targets of the virus.
- HIV-1 entry into target cells can occur via the plasma membrane or endosomes, but the specific pathways into primary CD4+ T cells are not fully understood.
Purpose of the Study:
- To investigate the mechanisms of HIV-1 entry into primary CD4+ T cells.
- To determine if macropinocytosis is involved in HIV-1 entry into primary CD4+ T cells.
Main Methods:
- Primary CD4+ T cells and T cell lines were used to study HIV-1 entry.
- Macropinocytosis was inhibited to assess its role in viral entry and infection.
- Microscopic analysis was performed to visualize viral fusion events.
Main Results:
- HIV-1 entry into primary CD4+ T cells occurred at both the plasma membrane and internal compartments, unlike T cell lines where entry was mainly at the plasma membrane.
- Inhibition of macropinocytosis significantly reduced HIV-1 internalization and fusion with primary CD4+ T cells, irrespective of coreceptor usage.
- HIV-1 fusion was confirmed to occur at the macropinosomal membrane.
- Blocking macropinocytosis effectively prevented HIV-1 infection of primary CD4+ T cells.
Conclusions:
- Macropinocytosis is identified as a significant pathway for HIV-1 entry into primary CD4+ T cells.
- Understanding this entry mechanism could inform therapeutic strategies against HIV-1 infection.
