Respiratory syncytial virus co-opts hypoxia-inducible factor-1α-mediated glycolysis to favor the production of infectious virus

mBio. 2023 Oct 31;14(5):e0211023. doi: 10.1128/mbio.02110-23. Epub 2023 Oct 5.

Abstract

Respiratory syncytial virus (RSV) is the leading etiological agent of lower respiratory tract illness. However, efficacious vaccines or antiviral drugs for treating RSV infections are currently not available. Indeed, RSV depends on host cells to provide energy needed to produce progeny virions. Glycolysis is a series of oxidative reactions used to metabolize glucose and provide energy to host cells. Therefore, glycolysis may be helpful for RSV infection. In this study, we show that RSV increases glycolysis by inducing the stabilization, transcription, translation, and activation of hypoxia-inducible factor (HIF)-1α in infected cells, which is important for the production of progeny RSV virions. This study contributes to understanding the molecular mechanism by which HIF-1α-mediated glycolysis controls RSV infection and reveals an effective target for the development of highly efficient anti-RSV drugs.

Keywords: HIF-1α; IR-PI3K-Akt signaling; ROS; glycolysis; mitochondria; respiratory syncytial virus.

MeSH terms

  • Communicable Diseases*
  • Glycolysis
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Respiratory Syncytial Virus Infections*
  • Respiratory Syncytial Virus, Human* / genetics

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit