You are here
HIV infection of dendritic cells subverts the IFN induction pathway via IRF-1 and inhibits type 1 IFN production.
Title | HIV infection of dendritic cells subverts the IFN induction pathway via IRF-1 and inhibits type 1 IFN production. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Harman, AN, Lai, J, Turville, S, Samarajiwa, S, Gray, L, Marsden, V, Mercier, SK, Mercier, S, Jones, K, Nasr, N, Rustagi, A, Cumming, H, Donaghy, H, Mak, J, Gale, M, Churchill, M, Hertzog, P, Cunningham, AL |
Journal | Blood |
Volume | 118 |
Issue | 2 |
Pagination | 298-308 |
Date Published | 2011 Jul 14 |
ISSN | 1528-0020 |
Keywords | Cells, Cultured, Dendritic Cells, Down-Regulation, Gene Expression Profiling, Gene Expression Regulation, HIV Infections, HIV-1, Humans, Interferon Regulatory Factor-1, Interferon Type I, Microarray Analysis, Promoter Regions, Genetic, Sequence Analysis, DNA, Signal Transduction, Up-Regulation |
Abstract | 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. |
DOI | 10.1182/blood-2010-07-297721 |
Alternate Journal | Blood |
PubMed ID | 21411754 |