HIF1α is required for NK cell metabolic adaptation during virus infection
- Washington University School of Medicine, United States
- Washington University, United States
- National Jewish Health, United States
- University of Iowa, United States
Abstract
Natural killer (NK) cells are essential for early protection against virus infection, and must metabolically adapt to the energy demands of activation. Here, we found upregulation of the metabolic adaptor hypoxia inducible factor-1α (HIF-1α) is a feature of mouse NK cells during murine cytomegalovirus (MCMV) infection in vivo. HIF-1 α -deficient NK cells failed to control viral load, causing increased morbidity. No defects were found in effector functions of HIF-1α KO NK cells however, their numbers were significantly reduced. Loss of HIF-1 α did not affect NK cell proliferation during in vivo infection and in vitro cytokine stimulation. Instead, we found HIF-1α -deficient NK cells showed increased expression of the pro-apoptotic protein Bim and glucose metabolism was impaired during cytokine stimulation in vitro. Similarly, during MCMV infection HIF-1α -deficient NK cells upregulated Bim and had increased caspase activity. Thus, NK cells require HIF-1α-dependent metabolic functions to repress Bim expression and sustain cell numbers for an optimal virus response.
Data availability
Data generated or analyzed during this study has been deposited to the Dryad Digital Depository, available here: doi:10.5061/dryad.n5tb2rbvm
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NK cell metabolic adaptation to infection promotes survival and viral clearanceDryad Digital Repository, doi:10.5061/dryad.n5tb2rbvm.
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HIF1α is required for NK cell metabolic adaptation during virus infectionhttps://creativecommons.org/publicdomain/zero/1.0/.
Article and author information
Author details
Francisco Victorino
Funding
National Institute of Environmental Health Sciences (R35ES028365)
- Gary Patti
National Institute of Allergy and Infectious Diseases (R01-AI131680)
- Wayne M Yokoyama
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Stipan Jonjic, University of Rijeka, Croatia
Ethics
Animal experimentation: All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#20180293) of the University of Washington in St. Louis School of Medicine.
Version history
- Received: March 17, 2021
- Preprint posted: March 19, 2021 (view preprint)
- Accepted: August 11, 2021
- Accepted Manuscript published: August 16, 2021 (version 1)
- Version of Record published: August 23, 2021 (version 2)
- Version of Record updated: August 25, 2021 (version 3)
- Version of Record updated: August 27, 2021 (version 4)
Copyright
© 2021, Victorino et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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HIF1α is required for NK cell metabolic adaptation during virus infection
eLife 10:e68484.
https://doi.org/10.7554/eLife.68484
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