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 κB sites in HIV-1 LTR or by suppressing activation of NF-κB. 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-κB pathway.
Hayashi
Takaya
T
Department of Immunotherapeutics, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Nishitsuji
Hironori
H
Takamori
Ayako
A
Hasegawa
Atsuhiko
A
Masuda
Takao
T
Kannagi
Mari
M
D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D016601:RNA-Binding Proteins; D014158:Transcription, Genetic; D014779:Virus Replication
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D016601:RNA-Binding Proteins; C485731:ZBP1 protein, human