{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T20:15:35Z","timestamp":1792959335315,"version":"4.5.0"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"21","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | NIH","doi-asserted-by":"publisher","award":["R01HD094937"],"award-info":[{"award-number":["R01HD094937"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | NIH","doi-asserted-by":"publisher","award":["R01HD094937"],"award-info":[{"award-number":["R01HD094937"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,5,27]]},"abstract":"<jats:p>\n                    Zika virus (ZIKV) infection can lead to a variety of clinical outcomes, including severe congenital abnormalities. The phosphatidylserine receptors AXL and TIM-1 are recognized as critical entry factors for ZIKV in vitro. However, it remains unclear whether and how ZIKV regulates these receptors during infection. In this study, we investigated AXL and TIM-1 expression in human lung adenocarcinoma epithelial A549 cells, glioblastoma U87 cells, and embryonic stem cell-derived trophoblasts following ZIKV infection. We found that both the Asian strain FSS13025 and the African strain MR766 of ZIKV downregulate AXL, with a milder effect on TIM-1. We identified several ZIKV proteins, notably envelope (E), NS2A, NS3, and NS4B, that contribute to this downregulation. Notably, treatment with lysosomal inhibitor NH\n                    <jats:sub>4<\/jats:sub>\n                    Cl or the autophagy inhibitor 3-methyladenine mitigated the AXL\/TIM-1 downregulation, indicating autophagy\u2019s involvement in the process. Importantly, this downregulation facilitates sustained viral replication and promotes viral spread by preventing superinfection and limiting cell death, which is also associated with impaired innate immune signaling. Our findings uncover a mechanism by which ZIKV downregulates entry factors to enhance prolonged viral replication and spread.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2427241122","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T13:45:08Z","timestamp":1748007908000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":18,"title":["Autophagy-mediated downregulation of AXL and TIM-1 promotes sustained Zika virus infection"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0775-6623","authenticated-orcid":false,"given":"Jingyou","family":"Yu","sequence":"first","affiliation":[{"name":"Center for Retrovirus Research, The Ohio State University","place":["Columbus"]},{"name":"Department of Veterinary Biosciences, The Ohio State University","place":["Columbus"]},{"name":"State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University","place":["Guangzhou, China"]},{"name":"Guangzhou National Laboratory","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9364-7636","authenticated-orcid":false,"given":"Yi-Min","family":"Zheng","sequence":"additional","affiliation":[{"name":"Center for Retrovirus Research, The Ohio State University","place":["Columbus"]},{"name":"Department of Veterinary Biosciences, The Ohio State University","place":["Columbus"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan A.","family":"Sheridan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Missouri","place":["Columbia"]},{"name":"Bond Life Sciences Center, University of Missouri","place":["Columbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Retrovirus Research, The Ohio State University","place":["Columbus"]},{"name":"Department of Veterinary Biosciences, The Ohio State University","place":["Columbus"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Ezashi","sequence":"additional","affiliation":[{"name":"Bond Life Sciences Center, University of Missouri","place":["Columbia"]},{"name":"Division of Animal Sciences, College of Agriculture, Food, and Natural Resources, University of Missouri","place":["Columbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0008-6559","authenticated-orcid":false,"given":"R. 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