HIF-1alpha-dependent gene expression program during the nucleic acid-triggered antiviral innate immune responses

Mol Cells. 2009 Feb 28;27(2):243-50. doi: 10.1007/s10059-009-0030-2. Epub 2009 Feb 20.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Antiviral Agents / metabolism*
  • Biomarkers / metabolism
  • Blotting, Western
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Hypoxia / drug effects
  • Gene Expression Profiling*
  • Glioblastoma / genetics*
  • Glioblastoma / immunology*
  • Glioblastoma / metabolism
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Poly I-C / pharmacology*
  • Poly dA-dT / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / pharmacology
  • RNA-Binding Proteins


  • Adaptor Proteins, Signal Transducing
  • Antiviral Agents
  • Biomarkers
  • Carrier Proteins
  • Glucose Transporter Type 1
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • IFIT1 protein, human
  • NF-kappa B
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • SLC2A1 protein, human
  • Poly dA-dT
  • Poly I-C