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Related Experiment Video

Updated: Aug 15, 2025

Immunometabolic Circuits in Infection for Advancing Host Directed Therapies
11:12

Immunometabolic Circuits in Infection for Advancing Host Directed Therapies

Published on: September 13, 2024

479

HIF-1α-Dependent Metabolic Reprogramming, Oxidative Stress, and Bioenergetic Dysfunction in SARS-CoV-2-Infected

Sirsendu Jana1, Michael R Heaven1, Charles B Stauft2

  • 1Laboratory of Biochemistry and Vascular Biology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.

International Journal of Molecular Sciences
|January 8, 2023
PubMed
Summary
This summary is machine-generated.

SARS-CoV-2 infection activates the hypoxia-inducible factor (HIF-1α) pathway, altering lung cell metabolism and causing inflammation. This HIF-1α activation contributes to bioenergetic dysfunction and metabolic reprogramming during COVID-19.

Keywords:
COVID-19 diseasebioenergeticshamsterhypoxiaproteomics

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Area of Science:

  • Molecular Biology
  • Immunology
  • Pathophysiology

Background:

  • The complex interactions between SARS-CoV-2 infection, inflammation, and oxygen balance remain unclear.
  • Understanding these mechanisms is crucial for developing effective COVID-19 treatments.

Purpose of the Study:

  • To investigate the role of hypoxia-inducible factor (HIF-1α) in SARS-CoV-2 infection.
  • To elucidate the impact of HIF-1α activation on lung cell metabolism and inflammation.

Main Methods:

  • Studied adult Syrian hamsters infected with SARS-CoV-2.
  • Analyzed HIF-1α pathway activation, including nuclear localization and target protein expression (Glut1, LDH, PDK1).
  • Measured glycolysis (ECAR) and mitochondrial respiration (OCR), and performed proteomic analysis.

Main Results:

  • SARS-CoV-2 infection activated HIF-1α in lung macrophages.
  • Increased glycolysis and reduced mitochondrial respiration were observed in infected lungs.
  • Deficits in mitochondrial ATP synthase and ATP/ADP translocase were identified.
  • HIF-1α activation correlated with increased inflammation and oxidative stress.

Conclusions:

  • HIF-1α acts as a central mediator in SARS-CoV-2 infection.
  • HIF-1α drives metabolic reprogramming, inflammation, and bioenergetic dysfunction in infected lungs.
  • Findings offer insights into COVID-19 pathogenesis and potential therapeutic targets.