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Updated: May 2, 2026
Analysis of SAMHD1 Restriction by Flow Cytometry in Human Myeloid U937 Cells
Published on: June 13, 2021
Moderate restriction of macrophage-tropic human immunodeficiency virus type 1 by SAMHD1 in monocyte-derived
Kahoru Taya1, Emi E Nakayama1, Tatsuo Shioda1
1Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Abstract:
Macrophage-tropic human immunodeficiency virus type 1 (HIV-1) strains are able to grow to high titers in human monocyte-derived macrophages. However, it was recently reported that cellular protein SAMHD1 restricts HIV-1 replication in human cells of the myeloid lineage, including monocyte-derived macrophages. Here we show that degradation of SAMHD1 in monocyte-derived macrophages was associated with moderately enhanced growth of the macrophage-tropic HIV-1 strain. SAMHD1 degradation was induced by treating target macrophages with vesicular stomatitis virus glycoprotein-pseudotyped human immunodeficiency virus type 2 (HIV-2) particles containing viral protein X. For undifferentiated monocytes, HIV-2 particle treatment allowed undifferentiated monocytes to be fully permissive for productive infection by the macrophage-tropic HIV-1 strain. In contrast, untreated monocytes were totally resistant to HIV-1 replication. These results indicated that SAMHD1 moderately restricts even a macrophage-tropic HIV-1 strain in monocyte-derived macrophages, whereas the protein potently restricts HIV-1 replication in undifferentiated monocytes.
Insights
Cellular protein SAMHD1 restricts HIV-1 replication. Degrading SAMHD1 in macrophages moderately enhanced HIV-1 growth, while it potently restricted HIV-1 in undifferentiated monocytes.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Macrophage-tropic human immunodeficiency virus type 1 (HIV-1) infects macrophages.
- Cellular protein SAMHD1 is known to restrict HIV-1 replication in myeloid cells.
- The precise role of SAMHD1 in HIV-1 replication within macrophages requires further elucidation.
Purpose of the Study:
- To investigate the role of SAMHD1 in restricting macrophage-tropic HIV-1 replication in monocyte-derived macrophages.
- To determine the effect of SAMHD1 degradation on HIV-1 permissiveness in macrophages and undifferentiated monocytes.
Main Methods:
- Treatment of monocyte-derived macrophages and undifferentiated monocytes with vesicular stomatitis virus glycoprotein-pseudotyped human immunodeficiency virus type 2 (HIV-2) particles containing viral protein X to induce SAMHD1 degradation.
- Assessing the replication of macrophage-tropic HIV-1 strains in treated and untreated cells.
- Comparing HIV-1 permissiveness in differentiated macrophages versus undifferentiated monocytes.
Main Results:
- Degradation of SAMHD1 in monocyte-derived macrophages led to moderately enhanced growth of macrophage-tropic HIV-1.
- HIV-2 particle treatment rendered undifferentiated monocytes fully permissive to macrophage-tropic HIV-1 infection.
- Untreated monocytes exhibited complete resistance to HIV-1 replication, highlighting potent SAMHD1 restriction.
Conclusions:
- SAMHD1 plays a role in restricting even macrophage-tropic HIV-1 strains in differentiated macrophages.
- SAMHD1 acts as a potent restriction factor against HIV-1 in undifferentiated monocytes.
- Modulating SAMHD1 levels can influence HIV-1 permissiveness in different myeloid cell states.
