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Here, we found upregulation of the metabolic adaptor hypoxia-inducible factor-1\u03b1 (HIF1\u03b1) is a feature of mouse NK cells during murine cytomegalovirus (MCMV) infection in vivo. HIF1\u03b1-deficient NK cells failed to control viral load, causing increased morbidity. No defects were found in effector functions of HIF1\u03b1KO NK cells; however, their numbers were significantly reduced. Loss of HIF1\u03b1 did not affect NK cell proliferation during in vivo infection and in vitro cytokine stimulation. Instead, we found that HIF1\u03b1-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 HIF1\u03b1-deficient NK cells upregulated Bim and had increased caspase activity. Thus, NK cells require HIF1\u03b1-dependent metabolic functions to repress Bim expression and sustain cell numbers for an optimal virus response.<\/jats:p>","DOI":"10.7554\/elife.68484","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T08:00:31Z","timestamp":1629100831000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.68484","source":"Crossref","is-referenced-by-count":24,"title":["HIF1\u03b1 is required for NK cell metabolic adaptation during virus infection"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7626-3219","authenticated-orcid":true,"given":"Francisco","family":"Victorino","sequence":"first","affiliation":[{"name":"Rheumatology Division, Washington University School of Medicine","place":["St. Louis, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tarin M","family":"Bigley","sequence":"additional","affiliation":[{"name":"Rheumatology Division, Washington University 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