title: HIF-1alpha-dependent gene expression program during the nucleic acid-triggered antiviral innate immune responses.
abstract: 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.
authors.affiliation: Department of Chemistry and Brain Korea 21 School of Chemical Materials Science, Sungkyunkwan University, Suwon, 440-746, Korea.
authors.forename: Sun Woo
authors.initials: SW
authors.lastname: Hong
authors.forename: Jae Wook
authors.initials: JW
authors.lastname: Yoo
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Kang
authors.forename: Soyoun
authors.initials: S
authors.lastname: Kim
authors.forename: Dong-Ki
authors.initials: DK
authors.lastname: Lee
mesh_terms: 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
chemical_list: 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