{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:47:49Z","timestamp":1782280069586,"version":"3.54.5"},"posted":{"date-parts":[[2025,6,24]]},"group-title":"Microbiology","reference-count":21,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,24]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Human phospholipid scramblase 1 (PLSCR1) is an interferon-stimulated gene (ISG) that inhibits viral infections through various mechanisms. Here, we identify PLSCR1 as a host restriction factor that inhibits HIV-1 entry by impairing membrane fusion mediated by the envelope glycoprotein (Env). Using multiple cell types including the human SupT1 T cell line and purified CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells, we demonstrate that PLSCR1 inhibits the replication of HIV-1 with diverse tropisms and subtypes, as well as HIV-2 and SIV. Mechanistically, we find that PLSCR1 blocks viral entry and cell-to-cell transmission by restricting HIV-1 virion-cell and cell-cell fusion without affecting CD4 or CXCR4 expression or virus binding to the cell surface. Notably, PLSCR1-mediated restriction of viral entry is independent of type I interferon signaling. Collectively, these findings establish PLSCR1 as a broad-spectrum lentiviral restriction factor that acts at the membrane fusion stage, thereby expanding our understanding of ISG-mediated antiviral defense.\n                <\/jats:p>","DOI":"10.1101\/2025.06.23.661195","type":"posted-content","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T14:50:16Z","timestamp":1750776616000},"source":"Crossref","is-referenced-by-count":0,"title":["IFN-inducible Human Phospholipid Scramblase 1 (PLSCR1) Protein Restricts HIV-1 Infection by Inhibiting Membrane Fusion"],"prefix":"10.64898","author":[{"given":"Yajie","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Min","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Hikichi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherimay","family":"Ablan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric O.","family":"Freed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1620-3817","authenticated-orcid":false,"given":"Shan-Lu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025062614151316000_2025.06.23.661195v1.1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.008193"},{"key":"2025062614151316000_2025.06.23.661195v1.2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006851"},{"key":"2025062614151316000_2025.06.23.661195v1.3","doi-asserted-by":"crossref","first-page":"e0134221","DOI":"10.1128\/spectrum.01342-21","article-title":"The Interferon-Inducible Human PLSCR1 Protein Is a Restriction Factor of Human Cytomegalovirus","volume":"10","year":"2022","journal-title":"Microbiol Spectr"},{"key":"2025062614151316000_2025.06.23.661195v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06322-y"},{"key":"2025062614151316000_2025.06.23.661195v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2012.01.010"},{"key":"2025062614151316000_2025.06.23.661195v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2012.06.019"},{"key":"2025062614151316000_2025.06.23.661195v1.7","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00895-3"},{"key":"2025062614151316000_2025.06.23.661195v1.8","doi-asserted-by":"publisher","DOI":"10.1021\/pr500943x"},{"key":"2025062614151316000_2025.06.23.661195v1.9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002767"},{"key":"2025062614151316000_2025.06.23.661195v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.02.098"},{"key":"2025062614151316000_2025.06.23.661195v1.11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005006"},{"key":"2025062614151316000_2025.06.23.661195v1.12","doi-asserted-by":"crossref","unstructured":"S. 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