HIV infection of dendritic cells subverts the IFN induction pathway via IRF-1 and inhibits type 1 IFN production
Andrew N Harman, Joey Lai, Stuart Turville, Shamith Samarajiwa, Lachlan Gray, Valerie Marsden, Sarah Mercier, Kate Jones, Najla Nasr, Arjun Rustagi, Helen Cumming, Heather Donaghy, Johnson Mak, Michael Gale, Melissa Churchill, Paul Hertzog, Anthony L Cunningham
Blood | AMER SOC HEMATOLOGY | Published : 2011
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 wit..View full abstract
Awarded by National Health and Medical Research Council (NHMRC)
Awarded by Cancer Research UK
Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
This work was supported by the National Health and Medical Research Council (NHMRC; program grant 358399).