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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Western
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Cell Differentiation / drug effects
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Gene Expression Regulation / drug effects
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Giant Cells / drug effects
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Giant Cells / pathology
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HIV Infections / pathology
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HIV Infections / virology
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HIV-1 / drug effects
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HIV-1 / physiology*
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HIV-2 / drug effects
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HIV-2 / physiology
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Humans
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Macrophage Colony-Stimulating Factor / pharmacology
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Macrophages / virology*
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Monocytes / pathology*
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Monomeric GTP-Binding Proteins / genetics
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Monomeric GTP-Binding Proteins / metabolism*
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Phosphorylation / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Small Interfering / metabolism
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SAM Domain and HD Domain-Containing Protein 1
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T-Lymphocytes / drug effects
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T-Lymphocytes / virology
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Vesiculovirus / drug effects
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Vesiculovirus / physiology
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Viral Tropism* / drug effects
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Virion / drug effects
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Virion / metabolism
Substances
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RNA, Messenger
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RNA, Small Interfering
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Macrophage Colony-Stimulating Factor
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SAM Domain and HD Domain-Containing Protein 1
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SAMHD1 protein, human
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Monomeric GTP-Binding Proteins
Grants and funding
This work was supported by a grant from the Ministry of Education, Culture, Sports, Science, and Technology, and by a grant from the Ministry of Health, Labour and Welfare, Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.