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In healthy blood donors, ZIKV RNA can be detected in red blood cells (RBCs) months after infection, clearance of detectable nucleic acid in plasma, and seroconversion. However, little information is available on the impact of ZIKV infection to metabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study design and methods<\/jats:title><jats:p>We applied mass spectrometry\u2013based metabolomics and lipidomics approaches to investigate the impact of ZIKV infection on RBCs over the course of infection. ZIKV\u2010infected blood donors (<jats:italic>n<\/jats:italic>\u00a0=\u00a025) were identified through molecular and serologic methods, which included nucleic acid amplification testing and real\u2010time polymerase chain reaction (PCR) for detection of ZIKV RNA and enzyme\u2010linked immunosorbent assay (ELISA) for detection of flavivirus\u2010specific IgM and IgG.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In ZIKV RNA\u2010positive donors, we observed lower glucose and lactate levels, and higher levels of ribose phosphate, suggestive of the activation of the pentose phosphate pathway. The top pathways altered in RBCs from ZIKV\u2010IgM\u2010positive donors include amino acid metabolism and biosynthesis, fatty acid metabolism and biosynthesis, linoleic acid and arachidonate metabolism and glutathione metabolism. RBCs from ZIKV\u2010infected donors had increased levels of early glycolytic metabolites, and higher levels of metabolites of the pentose phosphate pathway. Alterations in acyl\u2010carnitine and fatty acid metabolism are consistent with impaired membrane lipid homeostasis in RBCs from ZIKV IgM positive donors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>RBC from healthy blood donors who had been infected by ZIKV are characterized by long\u2010lasting metabolic alterations even months after infection has resolved.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.16851","type":"journal-article","created":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T11:52:39Z","timestamp":1647258759000},"page":"1045-1064","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Reprogramming of red blood cell metabolism in Zika virus\u2013infected donors"],"prefix":"10.1111","volume":"62","author":[{"given":"Alexis","family":"Catala","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics University of Colorado Anschutz Medical Campus  Aurora Colorado USA"},{"name":"Program in Structural Biology and Biochemistry University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mars","family":"Stone","sequence":"additional","affiliation":[{"name":"Vitalant Research Institute  San Francisco California USA"},{"name":"Department of Laboratory Medicine University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Busch","sequence":"additional","affiliation":[{"name":"Vitalant Research Institute  San Francisco California USA"},{"name":"Department of Laboratory Medicine University of California San Francisco  San Francisco California 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