{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T10:41:46Z","timestamp":1792233706640,"version":"4.4.0"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"37","license":[{"start":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T00:00:00Z","timestamp":1693872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2021-00993 2018-06156 2021-01756"],"award-info":[{"award-number":["2021-00993 2018-06156 2021-01756"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2018-05766 and 2017-03126"],"award-info":[{"award-number":["2018-05766 and 2017-03126"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,9,12]]},"abstract":"<jats:p>\n                    Crimean-Congo hemorrhagic fever (CCHF) caused by CCHF virus (CCHFV) is one of the epidemic-prone diseases prioritized by the World Health Organisation as public health emergency with an urgent need for accelerated research. The trajectory of host response against CCHFV is multifarious and remains unknown. Here, we reported the temporal spectrum of pathogenesis following the CCHFV infection using genome-wide blood transcriptomics analysis followed by advanced systems biology analysis, temporal immune-pathogenic alterations, and context-specific progressive and postinfection genome-scale metabolic models (GSMM) on samples collected during the acute (T0), early convalescent (T1), and convalescent-phase (T2). The interplay between the retinoic acid-inducible gene-I-like\/nucleotide-binding oligomerization domain-like receptor and tumor necrosis factor signaling governed the trajectory of antiviral immune responses. The rearrangement of intracellular metabolic fluxes toward the amino acid metabolism and metabolic shift toward oxidative phosphorylation and fatty acid oxidation during acute CCHFV infection determine the pathogenicity. The upregulation of the tricarboxylic acid cycle during CCHFV infection, compared to the noninfected healthy control and between the severity groups, indicated an increased energy demand and cellular stress. The upregulation of glycolysis and pyruvate metabolism potentiated energy generation through alternative pathways associated with the severity of the infection. The downregulation of metabolic processes at the convalescent phase identified by blood cell transcriptomics and single-cell type proteomics of five immune cells (CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, CD14\n                    <jats:sup>+<\/jats:sup>\n                    monocytes, B cells, and NK cells) potentially leads to metabolic rewiring through the recovery due to hyperactivity during the acute phase leading to post-viral fatigue syndrome.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2304722120","type":"journal-article","created":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T13:52:22Z","timestamp":1693921942000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":13,"title":["Systems-level temporal immune-metabolic profile in Crimean-Congo hemorrhagic fever virus infection"],"prefix":"10.1073","volume":"120","author":[{"given":"Anoop T.","family":"Ambikan","sequence":"first","affiliation":[{"name":"The Systems Virology Lab, Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, ANA Futura, Stockholm-14152, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9515-770X","authenticated-orcid":false,"given":"Nazif","family":"Elaldi","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Medical Faculty, Sivas Cumhuriyet University, Sivas 58140, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1086-5409","authenticated-orcid":false,"given":"Sara","family":"Svensson-Akusj\u00e4rvi","sequence":"additional","affiliation":[{"name":"The Systems Virology Lab, Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, ANA Futura, Stockholm-14152, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binnur","family":"Bagci","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Dietetics, Faculty of Health Sciences, Sivas Cumhuriyet University, Sivas, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5621-2844","authenticated-orcid":false,"given":"Ayse Nur","family":"Pektas","sequence":"additional","affiliation":[{"name":"Cumhuriyet University Advanced Technology Application and Research Center, Sivas Cumhuriyet University, Sivas 58140, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2273-3152","authenticated-orcid":false,"given":"Roger","family":"Hewson","sequence":"additional","affiliation":[{"name":"United Kingdom Health Security Agency, Porton Down, Salisbury, Wiltshire SP4 0JG, United Kingdom"},{"name":"Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4554-2391","authenticated-orcid":false,"given":"Gokhan","family":"Bagci","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Altinbas University, Istanbul 34147, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5931-419X","authenticated-orcid":false,"given":"Mehmet","family":"Arasli","sequence":"additional","affiliation":[{"name":"Department of Immunology, Medical Faculty, Bulent Ecevit University, Zonguldak 67600, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7381-3606","authenticated-orcid":false,"given":"Sofia","family":"Appelberg","sequence":"additional","affiliation":[{"name":"Public Health Agency of Sweden, Solna, Stockholm-17165, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4254-6090","authenticated-orcid":false,"given":"Adil","family":"Mardinoglu","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Kungliga Tekniska H\u00f6gskolan\u2013Royal Institute of Technology, Stockholm-17121, Sweden"},{"name":"Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral and Craniofacial Sciences, King\u2019s College London, London WC2R 2LS, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6128-4279","authenticated-orcid":false,"given":"Vikas","family":"Sood","sequence":"additional","affiliation":[{"name":"The Systems Virology Lab, Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, ANA Futura, Stockholm-14152, Sweden"},{"name":"Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard University, Delhi 110062, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1287-0906","authenticated-orcid":false,"given":"\u00c1kos","family":"V\u00e9gv\u00e1ri","sequence":"additional","affiliation":[{"name":"Division of Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm-17177, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Benfeitas","sequence":"additional","affiliation":[{"name":"The Systems Virology Lab, Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, ANA Futura, Stockholm-14152, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1136-3010","authenticated-orcid":false,"given":"Soham","family":"Gupta","sequence":"additional","affiliation":[{"name":"The Systems Virology Lab, Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, ANA Futura, Stockholm-14152, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilhan","family":"Cetin","sequence":"additional","affiliation":[{"name":"Department of Public Health, Medical Faculty, Sivas Cumhuriyet University, Sivas 58140, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Mirazimi","sequence":"additional","affiliation":[{"name":"Public Health Agency of Sweden, Solna, Stockholm-17165, Sweden"},{"name":"Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm-14152, Sweden"},{"name":"National Veterinary Institute, Uppsala-75189, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0844-3338","authenticated-orcid":false,"given":"Ujjwal","family":"Neogi","sequence":"additional","affiliation":[{"name":"The Systems Virology Lab, Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, ANA Futura, 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Ambikan Transcriptome-based systems-level temporal immune-metabolic profile in CCHF virus infection. NCBI BioProject. https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/PRJNA916211. Deposited 27 December 2022."},{"key":"e_1_3_4_52_2","unstructured":"A. Ambikan neogilab\/CCHF_GSMM: CCHF R Codes (Version cchf v1) [Computer software]. https:\/\/doi.org\/10.5281\/zenodo.8268766. Deposited 21 August 2023."},{"key":"e_1_3_4_53_2","doi-asserted-by":"crossref","unstructured":"Y. Perez-Riverol The PRIDE database resources in 2022: A Hub for mass spectrometry-based proteomics evidences. 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