DNA-dependent activator of IFN-regulatory factors enhances the transcription of HIV-1 through NF-κB

Pattern recognition receptors (PRRs) play a pivotal role in host innate immune responses against microbial infection Viruses are primarily recognized by PRRs such as Toll-like receptor 3 7 8 and 9 and RIG-I-like receptors Recent studies have demonstrated that DNA dependent activator of IFN-regulatory factors (DAI) is a cytosolic sensor molecule for dsDNA, and is implicated in antiviral responses to some DNA viruses Soon after infection human immunodeficiency virus type-1 (HIV-1) synthesizes viral dsDNA in the cytoplasm by reverse transcriptase In addition an immune compromised state due to chronic HIV-1 infection results in opportunistic infection with some microbes that potentially activate DAI However it has not been elucidated whether DAI affects HIV-1 replication or its possible mechanisms Here we showed that forced expression of DAI markedly enhanced HIV-1 replication which was largely impaired by mutations at kappa B sites in HIV-1 LTR or by suppressing activation of NF-kappa B Moreover Intact structure around the D3 region (174-232 aa) and two RIP homotypic interaction motifs (198-214 aa and 256-272 aa) within DAI were critical for its activity These results suggest that activation of DAI might contribute to augment HIV-1 replication through DAI-NF-kappa B pathway (C) 2010 Institut Pasteur Published by Elsevier Masson SAS All rights reserved