HIV-1 infection of human macrophages directly induces viperin which inhibits viral production.
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.
Centre for Virus Research, Westmead Millennium Institute, Westmead and the University of Sydney, Sydney, Australia.
Najla
N
Nasr
Susan
S
Maddocks
Stuart G
SG
Turville
Andrew N
AN
Harman
Natalie
N
Woolger
Karla J
KJ
Helbig
John
J
Wilkinson
Chris R
CR
Bye
Thomas K
TK
Wright
Dharshini
D
Rambukwelle
Heather
H
Donaghy
Michael R
MR
Beard
Anthony L
AL
Cunningham
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology; D005204:Farnesol / Q000494:pharmacology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D007372:Interferons / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D044925:Oxidoreductases Acting on CH-CH Group Donors; D017368:Protein Prenylation; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014779:Virus Replication; D000090123:Viperin Protein
D000998:Antiviral Agents; D015415:Biomarkers; D005204:Farnesol; D007372:Interferons; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011506:Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C444427:RSAD2 protein, human; D000090123:Viperin Protein