TY - JOUR
T1 - DNA-dependent activator of IFN-regulatory factors enhances the transcription of HIV-1 through NF-κB
AU - Hayashi, Takaya
AU - Nishitsuji, Hironori
AU - Takamori, Ayako
AU - Hasegawa, Atsuhiko
AU - Masuda, Takao
AU - Kannagi, Mari
N1 - Funding Information:
We thank Dr. S. Yamaoka for providing pSR-IκBα, Dr. I.S.Y. Chen for providing pNL4-3lucΔenv, pNL4-3thy1Δenv, pJD-1 and pHCMVG, and Dr. J. Fujisawa for providing κB-luc. This study was supported by grants from the Ministry of Health, Welfare and Labor of Japan and Japan Science Technology Agency .
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
KW - DAI
KW - HIV-1
KW - NF-κB
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U2 - 10.1016/j.micinf.2010.06.003
DO - 10.1016/j.micinf.2010.06.003
M3 - Article
C2 - 20599623
AN - SCOPUS:77958085761
SN - 1286-4579
VL - 12
SP - 937
EP - 947
JO - Microbes and Infection
JF - Microbes and Infection
IS - 12-13
ER -