{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T03:51:33Z","timestamp":1775879493122,"version":"3.50.1"},"posted":{"date-parts":[[2025,1,2]]},"group-title":"Microbiology","reference-count":70,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T00:00:00Z","timestamp":1735776000000},"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":[[2025,1,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>After decades of inactivity throughout the Americas, western equine encephalitis virus (WEEV) recently re-emerged in South America, causing a large-scale outbreak in humans and horses. WEEV binds protocadherin 10 (PCDH10) as a receptor; however, nonpathogenic strains no longer bind human or equine PCDH10 but retain the ability to bind avian receptors. Highly virulent WEEV strains can also bind the very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) as alternative receptors. Here, by determining cryo-electron microscopy structures of WEEV strains isolated from 1941\u20132005 bound to mammalian receptors, we identify polymorphisms in the WEEV spike protein that explain shifts in receptor dependencies and that can allow nonpathogenic strains to infect primary cortical neurons. We predict the receptor dependencies of additional strains and of a related North American alphavirus. Our findings have implications for outbreak preparedness and enhance understanding of arbovirus neurovirulence through virus receptor binding patterns.<\/jats:p>","DOI":"10.1101\/2025.01.01.631009","type":"posted-content","created":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T11:40:18Z","timestamp":1735818018000},"source":"Crossref","is-referenced-by-count":0,"title":["Molecular basis for shifted receptor recognition by an encephalitic arbovirus"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3181-9994","authenticated-orcid":false,"given":"Xiaoyi","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5964-1545","authenticated-orcid":false,"given":"Wanyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9424-7289","authenticated-orcid":false,"given":"Jessica","family":"Oros","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1950-7031","authenticated-orcid":false,"given":"Jesse S.","family":"Plung","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica A.","family":"Plante","sequence":"additional","affiliation":[{"name":"World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA"},{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA"},{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Himanish","family":"Basu","sequence":"additional","affiliation":[{"name":"Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4371-8090","authenticated-orcid":false,"given":"Sivapratha","family":"Nagappan-Chettiar","sequence":"additional","affiliation":[{"name":"Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua M.","family":"Boeckers","sequence":"additional","affiliation":[{"name":"Department of Neurology, F.M. 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