| First Author | Victorino F | Year | 2021 |
| Journal | Elife | Volume | 10 |
| PubMed ID | 34396954 | Mgi Jnum | J:311114 |
| Mgi Id | MGI:6765764 | Doi | 10.7554/eLife.68484 |
| Citation | Victorino F, et al. (2021) HIF1alpha is required for NK cell metabolic adaptation during virus infection. Elife 10:e68484 |
| abstractText | 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-1alpha (HIF1alpha) is a feature of mouse NK cells during murine cytomegalovirus (MCMV) infection in vivo. HIF1alpha-deficient NK cells failed to control viral load, causing increased morbidity. No defects were found in effector functions of HIF1alphaKO NK cells; however, their numbers were significantly reduced. Loss of HIF1alpha did not affect NK cell proliferation during in vivo infection and in vitro cytokine stimulation. Instead, we found that HIF1alpha-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 HIF1alpha-deficient NK cells upregulated Bim and had increased caspase activity. Thus, NK cells require HIF1alpha-dependent metabolic functions to repress Bim expression and sustain cell numbers for an optimal virus response. |
