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We found that the increase in type I interferon (IFN-I) in mice caused by infection with the Armstrong strain of lymphocytic choriomeningitis virus (LCMV; an arenavirus) reduced the megakaryocytic expression of genes encoding enzymes involved in lipid biosynthesis (\n            <jats:italic>cyclooxygenase 1<\/jats:italic>\n            and\n            <jats:italic>thromboxane A synthase 1<\/jats:italic>\n            ) and a thrombopoietic transcription factor (\n            <jats:italic>Nf-e2<\/jats:italic>\n            ). The decreased expression of these genes was associated with reduced numbers of circulating platelets and defects in the arachidonic acid synthetic pathway, thereby suppressing serotonin release from \u03b4-granules in platelets. Bleeding resulted when severe thrombocytopenia and altered platelet function reduced the amount of platelet-derived serotonin below a critical threshold. Bleeding was facilitated by the absence of the activity of the kinase Lyn or the administration of aspirin, an inhibitor of arachidonic acid synthesis. Mouse platelets were not directly affected by IFN-I because they lack the receptor for the cytokine (IFNAR1), suggesting that transfusion of normal platelets into LCMV-infected mice could increase the amount of platelet-released serotonin and help to control hemorrhage.\n          <\/jats:p>","DOI":"10.1126\/scisignal.abb0384","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T18:57:48Z","timestamp":1645556268000},"source":"Crossref","is-referenced-by-count":4,"title":["Arenaviral infection causes bleeding in mice due to reduced serotonin release from platelets"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2066-4536","authenticated-orcid":true,"given":"Roberto","family":"Aiolfi","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, MERU-Roon Research Center for Vascular Biology, Scripps Research, La Jolla, CA 92037, USA."},{"name":"Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy."},{"name":"Vita-Salute San Raffaele University, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4262-0406","authenticated-orcid":true,"given":"Giovanni","family":"Sitia","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9370-2671","authenticated-orcid":true,"given":"Matteo","family":"Iannacone","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy."},{"name":"Vita-Salute San Raffaele University, Milan, Italy."},{"name":"Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Brunetta","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, MERU-Roon Research Center for Vascular Biology, Scripps Research, La Jolla, CA 92037, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0205-2678","authenticated-orcid":true,"given":"Luca G.","family":"Guidotti","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy."},{"name":"Vita-Salute San Raffaele University, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0807-1295","authenticated-orcid":true,"given":"Zaverio M.","family":"Ruggeri","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, MERU-Roon Research Center for Vascular Biology, Scripps Research, La Jolla, CA 92037, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cll.2006.05.001"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2005.05.001"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2018.00232"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.17-0090"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2016.08.011"},{"key":"e_1_3_3_7_2","first-page":"29","article-title":"Understanding bleeding in Ebola virus disease","volume":"13","author":"McElroy A.","year":"2015","unstructured":"A. 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