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https://hdl.handle.net/2440/74112
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Type: | Journal article |
Title: | HIV-1 infection of human macrophages directly induces viperin which inhibits viral production |
Author: | Nasr, N. Maddocks, S. Turville, S. Harman, A. Woolger, N. Helbig, K. Wilkinson, J. Bye, C. Wright, T. Rambukwelle, D. Donaghy, H. Beard, M. Cunningham, A. |
Citation: | Blood, 2012; 120(4):778-788 |
Publisher: | Amer Soc Hematology |
Issue Date: | 2012 |
ISSN: | 0006-4971 1528-0020 |
Statement of Responsibility: | Najla Nasr, Susan Maddocks, Stuart G. Turville, Andrew N. Harman, Natalie Woolger, Karla J.Helbig, John Wilkinson, Chris R. Bye, Thomas K. Wright, Dharshini Rambukwelle, Heather Donaghy, Michael R. Beard and Anthony L. Cunningham |
Abstract: | Macrophages are key target cells for HIV-1. HIV-1BaL 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. |
Keywords: | Dendritic Cells Monocytes Macrophages Humans HIV-1 HIV Infections Farnesol Oxidoreductases Acting on CH-CH Group Donors Proteins Interferons RNA, Small Interfering RNA, Messenger Antiviral Agents Blotting, Western Immunoenzyme Techniques Oligonucleotide Array Sequence Analysis Flow Cytometry Gene Expression Profiling Mutagenesis, Site-Directed Reverse Transcriptase Polymerase Chain Reaction Immunoprecipitation Virus Replication Amino Acid Sequence Sequence Homology, Amino Acid Mutation Molecular Sequence Data Protein Prenylation Real-Time Polymerase Chain Reaction Biomarkers |
Rights: | © 2012 by The American Society of Hematology |
DOI: | 10.1182/blood-2012-01-407395 |
Published version: | http://dx.doi.org/10.1182/blood-2012-01-407395 |
Appears in Collections: | Aurora harvest 4 Microbiology and Immunology publications |
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