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HIF-1α-Dependent Gene Expression Program During the Nucleic Acid-Triggered Antiviral Innate Immune Responses

  • Hong, Sun Woo (Department of Chemistry and Brain Korea 21 School of Chemical Materials Science, Sungkyunkwan University) ;
  • Yoo, Jae Wook (Department of Chemistry and Brain Korea 21 School of Chemical Materials Science, Sungkyunkwan University) ;
  • Kang, Hye Suk (Department of Chemistry and Brain Korea 21 School of Chemical Materials Science, Sungkyunkwan University) ;
  • Kim, Soyoun (Department of Biomedical Engineeering, Dongguk University) ;
  • Lee, Dong-ki (Department of Chemistry and Brain Korea 21 School of Chemical Materials Science, Sungkyunkwan University)
  • Received : 2008.11.24
  • Accepted : 2008.12.06
  • Published : 2009.02.28

Abstract

Recent studies suggest a novel role of $HIF-1{\alpha}$ under nonhypoxic conditions, including antibacterial and antiviral innate immune responses. However, the identity of the pathogen-associated molecular pattern which triggers $HIF-1{\alpha}$ 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 $HIF-1{\alpha}$ protein level as well as the increase in $HIF-1{\alpha}$ 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 $HIF-1{\alpha}$ knock-down. Interestingly, $HIF-1{\alpha}$ knock-down also resulted in down-regulation of a number of genes involved in antiviral innate immune responses. Our study demonstrates that $HIF-1{\alpha}$ 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.

Keywords

Acknowledgement

Supported by : Korea Research Foundation

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