Contribution of hypoxia inducible factor-1 during viral infections

Virulence. 2020 Dec;11(1):1482-1500. doi: 10.1080/21505594.2020.1836904.

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that plays critical roles during the cellular response to hypoxia. Under normoxic conditions, its function is tightly regulated by the degradation of its alpha subunit (HIF-1α), which impairs the formation of an active heterodimer in the nucleus that otherwise regulates the expression of numerous genes. Importantly, HIF-1 participates in both cancer and infectious diseases unveiling new therapeutic targets for those ailments. Here, we discuss aspects related to the activation of HIF-1, the effects of this transcription factor over immune system components, as well as the involvement of HIF-1 activity in response to viral infections in humans. Although HIF-1 is currently being assessed in numerous clinical settings as a potential therapy for different diseases, up to date, there are no clinical studies evaluating the pharmacological modulation of this transcription factor as a possible new antiviral treatment. However, based on the available evidence, clinical trials targeting this molecule are likely to occur soon. In this review we discuss the role of HIF-1 in viral immunity, the modulation of HIF-1 by different types of viruses, as well as the effects of HIF-1 over their life cycle and the potential use of HIF-1 as a new target for the treatment of viral infections.

Keywords: DNA viruses; RNA viruses; hypoxia; normoxia; viral treatment; virus life cycle.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Hypoxia / physiology
  • Gene Expression Regulation
  • Humans
  • Hypoxia*
  • Hypoxia-Inducible Factor 1 / genetics*
  • Hypoxia-Inducible Factor 1 / metabolism
  • Virus Diseases / immunology*
  • Virus Diseases / physiopathology
  • Virus Diseases / therapy*

Substances

  • Hypoxia-Inducible Factor 1

Grants and funding

This work was supported by the Millenium Institute on immunology and Immunotherapy [P09/016-F; ICN09_016]; FONDECYT [1170964]; FONDECYT [1190830]; FONDECYT [1190864].