Related Experiment Video
Updated: Jun 6, 2026

Phagosome Migration and Velocity Measured in Live Primary Human Macrophages Infected with HIV-1
Published on: September 5, 2016
HIV-1 infects macrophages by exploiting an endocytic route dependent on dynamin, Rac1 and Pak1
Gemma C Carter1, Laura Bernstone, Darshan Baskaran
1Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Abstract:
Recent studies provide compelling evidence that HIV-1 entry in cell lines and lymphocytes proceeds by endocytosis, but these studies are still lacking in macrophages, an important natural target cell for HIV-1. Macrophages exhibit continual and extensive endocytic activity as part of their natural functions, so we investigated the uptake pathways involved in productive HIV-1 entry. We find that caveolae are not utilised by HIV-1, because the main structural proteins, caveolin-1 and 2 are absent from most human leukocytes. We then focused on macropinocytosis; we find that HIV-1 entry into macrophages is sensitive to inhibitors of Na(+)/H(+) exchange, actin rearrangement, dynamin, Rho family GTPases, and Pak1, but not to inhibitors of PI-3 kinase and myosin II. This leads us to conclude that HIV entry into macrophages proceeds by an endocytic pathway that is not classical macropinocytosis. Because of the limitations of a purely pharmacological study such as this, the final elucidation of this pathway awaits the development of reliable forward genetic approaches in authentic macrophages.
Insights
HIV-1 entry into macrophages uses an endocytic pathway distinct from classical macropinocytosis. This study investigates HIV uptake mechanisms in macrophages, crucial for understanding viral infection spread.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- HIV-1 infects macrophages, a critical cell type in viral pathogenesis.
- Previous studies established endocytosis for HIV-1 entry in lymphocytes but not macrophages.
- Macrophages possess high endocytic activity essential for their function.
Purpose of the Study:
- To investigate the specific endocytic pathways utilized by HIV-1 for entry into macrophages.
- To differentiate HIV-1 uptake mechanisms in macrophages from those in other cell types.
Main Methods:
- Pharmacological inhibition of key endocytic pathway components and cellular processes.
- Assessment of HIV-1 entry sensitivity to inhibitors of Na+/H+ exchange, actin rearrangement, dynamin, Rho GTPases, Pak1, PI-3 kinase, and myosin II.
- Analysis of caveolin-1 and caveolin-2 expression in human leukocytes.
Main Results:
- HIV-1 entry into macrophages is not mediated by caveolae due to the absence of caveolin-1 and -2 in most human leukocytes.
- HIV-1 entry is sensitive to inhibitors of Na+/H+ exchange, actin rearrangement, dynamin, Rho family GTPases, and Pak1.
- HIV-1 entry is not inhibited by PI-3 kinase or myosin II inhibitors.
Conclusions:
- HIV-1 entry into macrophages utilizes an endocytic pathway that differs from classical macropinocytosis.
- The precise endocytic pathway requires further elucidation through forward genetic approaches in macrophages.
Related Concept Videos
Inhibitors of Virion Maturation and Assembly
Size and Structure of Viral Genomes
Retrovirus Life Cycles
Retroviruses
Cancer Cell Migration through Invadopodia
Receptor-mediated Endocytosis

