{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T18:15:29Z","timestamp":1789236929412,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014144","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000}}],"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82302524"],"award-info":[{"award-number":["82302524"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Anhui procince","award":["2108085QC86"],"award-info":[{"award-number":["2108085QC86"]}]},{"name":"Scientific Program of Anhui Medical University","award":["2020xkj001"],"award-info":[{"award-number":["2020xkj001"]}]},{"name":"Basic - Clinical Collaborative Research Promotion Plan of Anhui Medical University","award":["2021xkjT021"],"award-info":[{"award-number":["2021xkjT021"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    SFTSV, a tick-borne bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS), exhibits symptoms such as thrombocytopenia, leukocytopenia, hemorrhage, disseminated intravascular coagulation, and even multiple-organ failure. Nevertheless, the underlying pathogenic pathways of this disease remain poorly understood. In this study, by utilizing a lethal mouse model of\n                    <jats:italic>IFNAR<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice, we discovered that complement hyperactivation occurs in the spleen, and the spleen serves as a source of the central complement component C3 in SFTSV-infected mice. Infection of spleen stromal fibroblastic reticular cells with SFTSV significantly induces intracellular complement pathways through a type I IFN-independent manner and generates the active component C3a through the alternative pathway. The transcription of\n                    <jats:italic>C3<\/jats:italic>\n                    and complement factor B (\n                    <jats:italic>Cfb<\/jats:italic>\n                    ) in SFTSV-infected fibroblastic reticular cells is regulated by C\/EBP-\u03b2. Administration of a C3aR antagonist leads to a reduction in virus load and the inflammatory response, alleviates spleen injury, and prolongs the survival time in\n                    <jats:italic>IFNAR<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>-\/-<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Collectively, our findings suggest that targeted complement therapy holds potential for the intervention of severe SFTS.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014144","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:57:31Z","timestamp":1776275851000},"page":"e1014144","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["C\/EBP-\u03b2-regulated complement hyperactivation in spleen of SFTSV-infected mice: A clue to targeted complement therapy"],"prefix":"10.1371","volume":"22","author":[{"given":"Yan","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xihua","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailin","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayue","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kehan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maozhang","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5560-6013","authenticated-orcid":true,"given":"Cong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"issue":"16","key":"ppat.1014144.ref001","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1056\/NEJMoa1010095","article-title":"Fever 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