HIF-1alpha-dependent gene expression program during the nucleic acid-triggered antiviral innate immune responses.
Recent studies suggest a novel role of HIF-1alpha under non-hypoxic conditions, including antibacterial and antiviral innate immune responses. However, the identity of the pathogen-associated molecular pattern which triggers HIF-1alpha activation during the antiviral response remains to be identified. Here, we demonstrate that cellular administration of double-stranded nucleic acids, the molecular mimics of viral genomes, results in the induction of HIF-1alpha protein level as well as the increase in HIF-1alpha target gene expression. Whole-genome DNA microarray analysis revealed that double-stranded nucleic acid treatment triggers induction of a number of hypoxia-inducible genes, and induction of these genes are compromised upon siRNA-mediated HIF-1alpha knock-down. Interestingly, HIF-1alpha knock-down also resulted in down-regulation of a number of genes involved in antiviral innate immune responses. Our study demonstrates that HIF-1alpha activation upon nucleic acid-triggered antiviral innate immune responses plays an important role in regulation of genes involved in not only hypoxic response, but also immune response.
Hong
Sun Woo
SW
Department of Chemistry and Brain Korea 21 School of Chemical Materials Science, Sungkyunkwan University, Suwon, 440-746, Korea.
Yoo
Jae Wook
JW
Kang
Hye Suk
HS
Kim
Soyoun
S
Lee
Dong-Ki
DK
D048868:Adaptor Proteins, Signal Transducing; D000998:Antiviral Agents / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011070:Poly I-C / Q000494:pharmacology*; D011067:Poly dA-dT / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D016601:RNA-Binding Proteins
D048868:Adaptor Proteins, Signal Transducing; D000998:Antiviral Agents; D015415:Biomarkers; D002352:Carrier Proteins; D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C484290:IFIT1 protein, human; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C495677:SLC2A1 protein, human; D011067:Poly dA-dT; D011070:Poly I-C