{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T17:02:06Z","timestamp":1789405326912,"version":"build-2803163510"},"reference-count":75,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI146342, U19 AI131130"],"award-info":[{"award-number":["R01AI146342, U19 AI131130"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM151043"],"award-info":[{"award-number":["R35GM151043"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,4,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>Zika virus (ZIKV) is spread by mosquito bites and is unique among known flaviviruses for being able to cause microcephaly. Entry factors for ZIKV are incompletely understood, but phosphatidylserine (PS) receptors, including the TAM (Tyro3, AXL, and Mer) and TIM (T-cell Ig mucin) families, can serve as cofactors for flavivirus entry in a cell type-specific manner. We identify AXL as the top hit in a CRISPR\/Cas9 genome-wide screen in human glioblastoma cells and establish a definitive role of AXL, but not TYRO3 or MerTK, for ZIKV infection. Additionally, Spondweni virus also shows AXL dependency, while dengue virus infection is not affected by AXL knockout. Passage of ZIKV in AXL knockout (KO) cells generated a mutant virus capable of infection via AXL-independent mechanisms, and multiple independent selections identified a common mutation, H83R, in the prM coding region of the ZIKV genome. The mutant virus exhibits an increased infectivity rate in AXL KO cells as compared to wild-type ZIKV and is dependent upon the single H83R mutation. The mutant virus\u2019 ability to infect cells in an AXL-independent manner is unrelated to interferon signaling antagonism but likely pertains to a change in virus maturation that leads to a structural disturbance of the ZIKV virion. Our study provides evidence for a potential mechanism linking the viral structural proteins and host PS receptor usage during flavivirus infection.<\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>A major challenge in elucidating the mechanism of Zika virus (ZIKV) pathogenesis is the multitude of cell types it infects with distinct requirements. The role of phosphatidylserine (PS) receptors in ZIKV infection is cell type-specific, and the controversy surrounds their function in flavivirus entry. Here, we establish a definitive requirement of AXL for infection of human glioblastoma cells by both Zika and Spondweni virus. We then identified a single amino acid mutation (H83R) in the prM protein of ZIKV that allowed AXL-independent infection of these cells. The H83R-mediated escape of AXL requirement is independent of interferon (IFN) signaling suppression by AXL; instead, the mutation has the potential to disrupt the virus assembly and virion structure. This study reveals a previously unknown connection between the PS receptor usage and the flavivirus prM gene, which can guide detailed molecular mechanism studies of the interplay between virion assembly and virus entry.<\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/jvi.01873-24","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T14:00:37Z","timestamp":1741615237000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["A single mutation in the PrM gene of Zika virus determines AXL dependency for infection of human neural cells"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4592-0321","authenticated-orcid":false,"given":"Renu","family":"Khasa","sequence":"first","affiliation":[{"name":"Department of Biological Science, Florida State University","place":["Tallahassee, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah C.","family":"Ogden","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Florida State University","place":["Tallahassee, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5551-3469","authenticated-orcid":true,"given":"Yuqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Florida State University","place":["Tallahassee, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongiun","family":"Mou","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Case Western Reserve University","place":["Cleveland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna D.","family":"Metzler","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Florida State University","place":["Tallahassee, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0918-016X","authenticated-orcid":true,"given":"Xuping","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston","place":["Galveston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghong","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Case Western Reserve University","place":["Cleveland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-410X","authenticated-orcid":true,"given":"Hengli","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Florida State University","place":["Tallahassee, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Fileds virology","author":"Pierson TC","year":"2013","unstructured":"Pierson TC, Diamond MS. 2013. Flaviviruses. In Fileds virology"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005083"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(52)90042-4"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0446-y"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix515"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.06.028"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature18625"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature18631"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1900867116"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2019.11.016"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90167-X"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.11.10.5016-5031.1991"},{"key":"e_1_3_2_14_2","first-page":"647","article-title":"Cloning and mRNA expression analysis of a novel human protooncogene, c-mer","volume":"5","author":"Graham DK","year":"1994","unstructured":"Graham DK, Dawson TL, Mullaney DL, Snodgrass HR, Earp HS. 1994. Cloning and mRNA expression analysis of a novel human protooncogene, c-mer. Cell Growth Differ 5:647\u2013657.","journal-title":"Cell Growth Differ"},{"key":"e_1_3_2_15_2","first-page":"2567","article-title":"Structure, expression, and activity of Tyro 3, a neural adhesion-related receptor tyrosine kinase","volume":"9","author":"Lai C","year":"1994","unstructured":"Lai C, Gore M, Lemke G. 1994. Structure, expression, and activity of Tyro 3, a neural adhesion-related receptor tyrosine kinase. Oncogene 9:2567\u20132578.","journal-title":"Oncogene"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.39.22681"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.47.30022"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90520-0"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.16.9785"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/373623a0"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.309866"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.07.002"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.11.011"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.03.012"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2017.07.012"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1620558114"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.08.079"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/emi.2017.10"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.000886"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.03.058"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep44286"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.12.045"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-017-0092-4"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01372-19"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102471"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01018-18"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00705-21"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2021.11.001"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2018.03.009"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.08.009"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.03.012"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02079-20"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.07.005"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.3390\/v12050579"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.2017109309122017c"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01683-18"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuros\/nyy047"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-3201"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021840"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M504337200"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.11.042"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02134-16"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3047"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.05.004"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.02.003"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-017-0092-4"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature17994"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf5316"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2018.05.006"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2303"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1247005"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00354-15"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.3390\/v6010069"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.03.051"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.24037"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.052613-0"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2019.1590130"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.71.11.8475-8481.1997"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1153264"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3352"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31111-y"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4877"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2006.07.011"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2020.09.001"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0554-4"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4169"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.01873-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.01873-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T13:03:30Z","timestamp":1744722210000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jvi.01873-24"}},"subtitle":[],"editor":[{"given":"Guangxiang George","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,4,15]]},"references-count":75,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4,15]]}},"alternative-id":["10.1128\/jvi.01873-24"],"URL":"https:\/\/doi.org\/10.1128\/jvi.01873-24","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,15]]},"assertion":[{"value":"2024-10-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01873-24"}}