HIV infection of dendritic cells subverts the IFN induction pathway via IRF-1 and inhibits type 1 IFN production

Harman, Andrew N., Lai, Joey, Turville, Stuart, Samarajiwa, Shamith, Gray, Lachlan, Marsden, Valerie, Mercier, Sarah, Jones, Kate, Nasr, Najla, Cumming, Helen, Donaghy, Heather, Mak, Johnson, Churchill, Melissa, Hertzog, Paul and Cunningham, Anthony L. 2011, HIV infection of dendritic cells subverts the IFN induction pathway via IRF-1 and inhibits type 1 IFN production, Blood, vol. 118, no. 26, pp. 298-308, doi: 10.1182/blood-2010-07-297721.

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Title HIV infection of dendritic cells subverts the IFN induction pathway via IRF-1 and inhibits type 1 IFN production
Author(s) Harman, Andrew N.
Lai, Joey
Turville, Stuart
Samarajiwa, Shamith
Gray, Lachlan
Marsden, Valerie
Mercier, Sarah
Jones, Kate
Nasr, Najla
Cumming, Helen
Donaghy, Heather
Mak, JohnsonORCID iD for Mak, Johnson
Churchill, Melissa
Hertzog, Paul
Cunningham, Anthony L.
Journal name Blood
Volume number 118
Issue number 26
Start page 298
End page 308
Total pages 11
Publisher American Society of Hematology
Place of publication Washington, D. C.
Publication date 2011-12-22
ISSN 0006-4971
Keyword(s) viruses
Summary Many viruses have developed mechanisms to evade the IFN response. Here, HIV-1 was shown to induce a distinct subset of IFN-stimulated genes (ISGs) in monocyte-derived dendritic cells (DCs), without detectable type I or II IFN. These ISGs all contained an IFN regulatory factor 1 (IRF-1) binding site in their promoters, and their expression was shown to be driven by IRF-1, indicating this subset was induced directly by viral infection by IRF-1. IRF-1 and -7 protein expression was enriched in HIV p24 antigen-positive DCs. A HIV deletion mutant with the IRF-1 binding site deleted from the long terminal repeat showed reduced growth kinetics. Early and persistent induction of IRF-1 was coupled with sequential transient up-regulation of its 2 inhibitors, IRF-8, followed by IRF-2, suggesting a mechanism for IFN inhibition. HIV-1 mutants with Vpr deleted induced IFN, showing that Vpr is inhibitory. However, HIV IFN inhibition was mediated by failure of IRF-3 activation rather than by its degradation, as in T cells. In contrast, herpes simplex virus type 2 markedly induced IFNβ and a broader range of ISGs to higher levels, supporting the hypothesis that HIV-1 specifically manipulates the induction of IFN and ISGs to enhance its noncytopathic replication in DCs.
Language eng
DOI 10.1182/blood-2010-07-297721
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2011, American Society of Hematology
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Document type: Journal Article
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School of Medicine
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