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Harold & Leila Y. Mathers Foundation"},{"DOI":"10.13039\/501100000854","name":"International Human Frontier Science Program Organization","doi-asserted-by":"crossref","award":["RGP011\/2023"],"award-info":[{"award-number":["RGP011\/2023"]}],"id":[{"id":"10.13039\/501100000854","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,28]]},"abstract":"<jats:p>\n                  Arthritogenic alphaviruses cause acute febrile illnesses associated with rash and arthritis when they are transmitted to humans through the bite of infected mosquitoes. Among these, chikungunya virus (CHIKV), transmitted primarily through the bite of infected\n                  <jats:italic>Aedes aegypti<\/jats:italic>\n                  and\n                  <jats:italic>Aedes albopictus<\/jats:italic>\n                  mosquitoes, causes explosive outbreaks involving hundreds of thousands to millions of cases, with recent re-emergence in several global regions. While several cellular receptors that mediate alphavirus entry into mammalian cells have been identified, their mosquito counterparts remained unknown, largely due to a lack of functional genomics tools for these invertebrate species. Here, we established a CRISPR-based genetic screening platform in\n                  <jats:italic>Aedes albopictus<\/jats:italic>\n                  cells and used it to identify Lachesin, a conserved invertebrate cell adhesion molecule, as a receptor for CHIKV and multiple related alphaviruses including Semliki Forest virus (SFV), o\u2019nyong-nyong virus (ONNV), Mayaro virus (MAYV), and Ross River virus (RRV). Lachesin depletion using RNA interference, anti-Lachesin antibody treatment, and soluble forms of Lachesin blocked CHIKV and SFV E2\u2013E1 glycoprotein-mediated infection of mosquito cells. We show that alphavirus E2\u2013E1 glycoproteins bind the first immunoglobulin domain of Lachesin, facilitating attachment and internalization of virus-like particles. Orthologs from divergent mosquito genera, but not from arachnids or other arthropods, also serve as alphavirus receptors, suggesting that cellular receptor binding is not the main obstacle to arthritogenic alphavirus vector host expansion. Our findings enhance understanding of the mechanisms of alphavirus emergence and vector competence and could aid in the development of broadly active, entry-targeted therapeutics against multiple alphaviruses that threaten public health.\n                <\/jats:p>","DOI":"10.64898\/2026.07.28.741058","type":"posted-content","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:30:12Z","timestamp":1785299412000},"source":"Crossref","is-referenced-by-count":2,"title":["Lachesin is a mosquito receptor for multiple arthritogenic alphaviruses"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1950-7031","authenticated-orcid":false,"given":"Jesse S.","family":"Plung","sequence":"first","affiliation":[{"name":"Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0172-8090","authenticated-orcid":false,"given":"Enzo","family":"Mameli","sequence":"additional","affiliation":[{"name":"Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5202-4475","authenticated-orcid":false,"given":"Anja C. M.","family":"de Bruin","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical University of Innsbruck, Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4768-7458","authenticated-orcid":false,"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":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3181-9994","authenticated-orcid":false,"given":"Xiaoyi","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2888-8665","authenticated-orcid":false,"given":"Biswajit","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1786-9437","authenticated-orcid":false,"given":"Bailey C.","family":"Willett","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T. 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Chan School of Public Health, Boston, MA, USA"},{"name":"Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1494-1402","authenticated-orcid":false,"given":"Yanhui","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellie M.","family":"Hajovsky","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":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8558-8007","authenticated-orcid":false,"given":"Haley","family":"Varnum","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9482-964X","authenticated-orcid":false,"given":"Praju V.","family":"Anekal","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA"},{"name":"MicRoN Core, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Thornburg","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T. 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