{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:35:06Z","timestamp":1787240106379,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T00:00:00Z","timestamp":1659916800000},"content-version":"am","delay-in-days":365,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T00:00:00Z","timestamp":1628380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR073172"],"award-info":[{"award-number":["AR073172"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM109091"],"award-info":[{"award-number":["P20GM109091"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL131667"],"award-info":[{"award-number":["HL131667"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["w81xwh1810096"],"award-info":[{"award-number":["w81xwh1810096"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) plays a crucial role in mediating viral entry into host cells. However, whether it contributes to pulmonary hyperinflammation in patients with coronavirus disease 2019 is not well known. In this study, we developed a spike protein\u2013pseudotyped (Spp) lentivirus with the proper tropism of the SARS\u2010CoV\u20102 spike protein on the surface and determined the distribution of the Spp lentivirus in wild\u2010type C57BL\/6J male mice that received an intravenous injection of the virus. Lentiviruses with vesicular stomatitis virus glycoprotein (VSV\u2010G) or with a deletion of the receptor\u2010binding domain (RBD) in the spike protein [Spp (\u2206RBD)] were used as controls. Two hours postinfection (hpi), there were 27\u201075 times more viral burden from Spp lentivirus in the lungs than in other organs; there were also about 3\u20105 times more viral burden from Spp lentivirus than from VSV\u2010G lentivirus in the lungs, liver, kidney, and spleen. Deletion of RBD diminished viral loads in the lungs but not in the heart. Acute pneumonia was observed in animals 24 hpi. Spp lentivirus was mainly found in SPC\n                    <jats:sup>+<\/jats:sup>\n                    and LDLR\n                    <jats:sup>+<\/jats:sup>\n                    pneumocytes and macrophages in the lungs. IL6, IL10, CD80, and PPAR\u2010\u03b3 were quickly upregulated in response to infection in the lungs as well as in macrophage\u2010like RAW264.7 cells. Furthermore, forced expression of the spike protein in RAW264.7 cells significantly increased the mRNA levels of the same panel of inflammatory factors. Our results demonstrated that the spike protein of SARS\u2010CoV\u20102 confers the main point of viral entry into the lungs and can induce cellular pathology. Our data also indicate that an alternative ACE2\u2010independent viral entry pathway may be recruited in the heart and aorta.\n                  <\/jats:p>","DOI":"10.1096\/fj.202002742rr","type":"journal-article","created":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T05:08:16Z","timestamp":1628399296000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Spike protein of SARS\u2010CoV\u20102 activates macrophages and contributes to induction of acute lung inflammation in male mice"],"prefix":"10.1096","volume":"35","author":[{"given":"Xiaoling","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Anatomy School of Medicine University of South Carolina Columbia SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Anatomy School of Medicine University of South 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Computing University of South Carolina Columbia SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,8]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"COVID\u201019 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU)","author":"CoronavirusResourceCenter","year":"2020"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/s41564-020-0695-z","article-title":"The species Severe acute respiratory syndrome\u2010related coronavirus: classifying 2019\u2010nCoV and naming it SARS\u2010CoV\u20102","volume":"5","author":"Coronaviridae Study Group of the International Committee on Taxonomy of Viruses","year":"2020","journal-title":"Nat Microbiol"},{"issue":"7836","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41586-020-2951-z","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat 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