Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
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
Statement of
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; Proteins; Interferons; RNA, Small Interfering; RNA, Messenger; Biological Markers; 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
Rights: © 2012 by The American Society of Hematology
RMID: 0020121421
DOI: 10.1182/blood-2012-01-407395
Appears in Collections:Microbiology and Immunology publications

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.