Abstract
Macrophages are key target cells for HIV-1. HIV-1(BaL) induced a subset of interferon-stimulated genes in monocyte-derived macrophages (MDMs), which differed from that in monocyte-derived dendritic cells and CD4 T cells, without inducing any interferons. Inhibition of type I interferon induction was mediated by HIV-1 inhibition of interferon-regulated factor (IRF3) nuclear translocation. In MDMs, viperin was the most up-regulated interferon-stimulated genes, and it significantly inhibited HIV-1 production. HIV-1 infection disrupted lipid rafts via viperin induction and redistributed viperin to CD81 compartments, the site of HIV-1 egress by budding in MDMs. Exogenous farnesol, which enhances membrane protein prenylation, reversed viperin-mediated inhibition of HIV-1 production. Mutagenesis analysis in transfected cell lines showed that the internal S-adenosyl methionine domains of viperin were essential for its antiviral activity. Thus viperin may contribute to persistent noncytopathic HIV-1 infection of macrophages and possibly to biologic differences with HIV-1-infected T cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Antiviral Agents / metabolism
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Biomarkers / metabolism
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Blotting, Western
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Dendritic Cells / cytology
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Dendritic Cells / metabolism
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Dendritic Cells / virology
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Farnesol / pharmacology
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Flow Cytometry
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Gene Expression Profiling
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HIV Infections / metabolism
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HIV Infections / pathology
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HIV Infections / virology*
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HIV-1 / genetics
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HIV-1 / pathogenicity*
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Humans
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Immunoenzyme Techniques
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Immunoprecipitation
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Interferons / metabolism
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Macrophages / cytology
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Macrophages / metabolism
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Macrophages / virology*
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Molecular Sequence Data
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Monocytes / cytology
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Monocytes / metabolism
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Monocytes / virology*
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Mutagenesis, Site-Directed
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Mutation / genetics
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Oligonucleotide Array Sequence Analysis
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Oxidoreductases Acting on CH-CH Group Donors
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Protein Prenylation
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Proteins / antagonists & inhibitors
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Proteins / genetics
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Proteins / metabolism*
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RNA, Messenger / genetics
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RNA, Small Interfering / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Homology, Amino Acid
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Virus Replication*
Substances
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Antiviral Agents
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Biomarkers
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Proteins
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RNA, Messenger
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RNA, Small Interfering
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Farnesol
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Interferons
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Oxidoreductases Acting on CH-CH Group Donors
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RSAD2 protein, human