{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:40:32Z","timestamp":1790800832921,"version":"4.1.0"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"EC | European Research Council","award":["101019724 EVADER"],"award-info":[{"award-number":["101019724 EVADER"]}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"crossref","award":["PID2020 118602RB I00 ZooVir"],"award-info":[{"award-number":["PID2020 118602RB I00 ZooVir"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100004410","name":"European Molecular Biology Organization","doi-asserted-by":"crossref","award":["Postdoctoral fellowship ALTF 140 2021"],"award-info":[{"award-number":["Postdoctoral fellowship ALTF 140 2021"]}],"id":[{"id":"10.13039\/100004410","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2024,4,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>SARS-CoV-2 infects both the upper and lower respiratory tracts, which are characterized by different temperatures (33\u00b0C and 37\u00b0C, respectively). In addition, fever is a common COVID-19 symptom. SARS-CoV-2 has been shown to replicate more efficiently at low temperatures, but the effect of temperature on different viral proteins remains poorly understood. Here, we investigate how temperature affects the SARS-CoV-2 spike function and evolution. We first observed that increasing temperature from 33\u00b0C to 37\u00b0C or 39\u00b0C increased spike-mediated cell\u2013cell fusion. We then experimentally evolved a recombinant vesicular stomatitis virus expressing the SARS-CoV-2 spike at these different temperatures. We found that spike-mediated cell\u2013cell fusion was maintained during evolution at 39\u00b0C but was lost in a high proportion of viruses that evolved at 33\u00b0C or 37\u00b0C. Consistently, sequencing of the spikes evolved at 33\u00b0C or 37\u00b0C revealed the accumulation of mutations around the furin cleavage site, a region that determines cell\u2013cell fusion, whereas this did not occur in spikes evolved at 39\u00b0C. Finally, using site-directed mutagenesis, we found that disruption of the furin cleavage site had a temperature-dependent effect on spike-induced cell\u2013cell fusion and viral fitness. Our results suggest that variations in body temperature may affect the activity and diversification of the SARS-CoV-2 spike.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      When it infects humans, SARS-CoV-2 is exposed to different temperatures (e.g., replication site and fever). Temperature has been shown to strongly impact SARS-CoV-2 replication, but how it affects the activity and evolution of the spike protein remains poorly understood. Here, we first show that high temperatures increase the SARS-CoV-2 spike fusogenicity. Then, we demonstrate that the evolution of the spike activity and variants depends on temperature. Finally, we show that the functional effect of specific spike mutations is temperature-dependent. Overall, our results suggest that temperature may be a factor influencing the activity and adaptation of the SARS-CoV-2 spike\n                      <jats:italic>in vivo<\/jats:italic>\n                      , which will help understanding viral tropism, pathogenesis, and evolution.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.03360-23","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T11:24:21Z","timestamp":1709033061000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Temperature impacts SARS-CoV-2 spike fusogenicity and evolution"],"prefix":"10.1128","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4963-1378","authenticated-orcid":true,"given":"J\u00e9r\u00e9my","family":"Dufloo","sequence":"first","affiliation":[{"name":"Institute for Integrative Systems Biology, Consejo Superior de Investigaciones Cient\u00edficas-Universitat de Val\u00e8ncia, Paterna, Val\u00e8ncia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1844-545X","authenticated-orcid":false,"given":"Rafael","family":"Sanju\u00e1n","sequence":"additional","affiliation":[{"name":"Institute for Integrative Systems Biology, Consejo Superior de Investigaciones Cient\u00edficas-Universitat de Val\u00e8ncia, Paterna, Val\u00e8ncia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-021-00249-2"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI148517"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104232"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-020-00459-7"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001158"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2218083120"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001065"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02021-22"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/v14102178"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101151"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020107405"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2021.167280"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03491-6"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00474-22"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009246"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-021-00573-0"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2021108944"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04474-x"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.04.035"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04462-1"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(23)00100-3"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.06.020"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201181"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.06.021"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.61312"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0265453"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","unstructured":"Carrascosa-S\u00e0ez M Marqu\u00e9s M-C Geller R Elena SF Rahmeh A Dufloo J Sanju\u00e1n R The IBV-Covid19-Pipeline. 2023. 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