{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:19:01Z","timestamp":1786987141611,"version":"build-2736575974"},"posted":{"date-parts":[[2025,10,24]]},"group-title":"Immunology","reference-count":69,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH","award":["R01 AI149486"],"award-info":[{"award-number":["R01 AI149486"]}]},{"name":"NIH","award":["5U19AI057266-316 13REVIS Supplement"],"award-info":[{"award-number":["5U19AI057266-316 13REVIS Supplement"]}]},{"DOI":"10.13039\/501100009053","name":"Wellcome Trust\/DBT India Alliance","doi-asserted-by":"crossref","award":["Early Career Fellowship grant IA\/E\/18\/1\/504307"],"award-info":[{"award-number":["Early Career Fellowship grant IA\/E\/18\/1\/504307"]}],"id":[{"id":"10.13039\/501100009053","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,24]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  Zika virus (ZIKV) can be vertically transmitted from a pregnant mother to the developing fetus, resulting in microcephaly and\/or other congenital malformations. Dengue virus (DENV) cross-reactive antibodies can facilitate ZIKV placental transcytosis and enhance ZIKV infection of placenta macrophage-Hofbauer cells through binding to Fc-\u03b3 receptors (Fc\u03b3Rs). To understand the role of individual Fc\u03b3R in antibody-mediated ZIKV placental infection, we generated a comprehensive panel of Fc-variants spanning a wide range of binding affinities to different Fc\u03b3Rs. We found that mutations with increased affinity to Fc\u03b3RI strongly correlated with an increased frequency of infected pro-monocytic U937 and Hofbauer cells. Next, we genetically deleted individual Fc\u03b3R in U937 cells, and found that the knockout of\n                  <jats:italic>FCGR1A<\/jats:italic>\n                  gene completely abolished ZIKV infection. In contrast, the deletion of\n                  <jats:italic>FCGR2B<\/jats:italic>\n                  gene showed no effect on ZIKV infection, and the deletion of\n                  <jats:italic>FCGR2A<\/jats:italic>\n                  gene had only a moderate impact on ZIKV infection. We further observed that Fc\u03b3RI was involved in both increased ZIKV internalization and replication. Collectively, our results establish Fc\u03b3RI as the key Fc receptor responsible for antibody-mediated ZIKV infection in both U937 and primary placental macrophages. These mechanistic findings not only provide insight into the importance of Fc\u03b3RI in ZIKV vertical transmission but also highlight Fc\u03b3RI as a potential therapeutic target, with significant implications for the development of strategies to prevent ZIKV transmission from mother to fetus.\n                <\/jats:p>","DOI":"10.1101\/2025.10.23.684201","type":"posted-content","created":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:15:31Z","timestamp":1761351331000},"source":"Crossref","is-referenced-by-count":2,"title":["Fc\u03b3RI is the key determinant of antibody-mediated Zika virus infection of human placental macrophages"],"prefix":"10.64898","author":[{"given":"Lingling","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn M.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob W.","family":"Vander Velden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faith A.","family":"Mbadugha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Hailstorks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Sundberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego 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