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Recently, we identified low-density lipoprotein receptor related protein 1 (Lrp1) as a host entry factor for two other bunyaviruses Rift Valley fever virus (RVFV) and Oropouche virus (OROV). Here, we assessed the role of Lrp1 in mediating JCV cellular infection of neurons. Both neuronal and non-neuronal immortalized cell lines deficient for Lrp1 displayed reduction in infection with JCV, and early stages of infection such as binding and internalization were impacted by lack of Lrp1. In primary rat neurons, Lrp1 was highly expressed, and the neurons were highly permissive for JCV infection. Treatment of primary neurons with recombinant receptor-associated protein (RAP), a high affinity ligand for Lrp1, resulted in reduced infectivity with JCV. In addition, pretreatment of cells with RVFV Gn inhibited JCV infection, suggesting that the two viruses may share overlapping binding sites. These results provide compelling evidence that Lrp1 is an important cellular factor for efficient infection by JCV, and thus multiple bunyaviruses with varying clinical manifestations and tissue tropism are facilitated by the host cell Lrp1. Reliance of multiple bunyaviruses on Lrp1 makes it a promising target for pan-bunyaviral antivirals and therapeutics.<\/jats:p>","DOI":"10.1101\/2024.11.06.622176","type":"posted-content","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T22:10:15Z","timestamp":1730931015000},"source":"Crossref","is-referenced-by-count":3,"title":["Lrp1 facilitates infection of neurons by Jamestown Canyon virus"],"prefix":"10.64898","author":[{"given":"Zachary D.","family":"Frey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Price","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaleigh A.","family":"Connors","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael E.","family":"Rush","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Griffin","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cade E.","family":"Sterling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farheen","family":"Fatma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline M.","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safder","family":"Ganaie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxia","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary P.","family":"Wills","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy W.","family":"Leung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaya K.","family":"Amarasinghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0857-2973","authenticated-orcid":false,"given":"Amy L.","family":"Hartman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024111108351623000_2024.11.06.622176v1.1","doi-asserted-by":"publisher","DOI":"10.3201\/eid2901.220154"},{"key":"2024111108351623000_2024.11.06.622176v1.2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1986.35.1285"},{"key":"2024111108351623000_2024.11.06.622176v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-1702(99)00033-7"},{"key":"2024111108351623000_2024.11.06.622176v1.4","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1986.35.376"},{"key":"2024111108351623000_2024.11.06.622176v1.5","doi-asserted-by":"publisher","DOI":"10.3201\/eid2401.170484"},{"key":"2024111108351623000_2024.11.06.622176v1.6","first-page":"593","article-title":"Serologic Survey of Mosquito-Borne Viruses in Hunter-Harvested White-Tailed Deer (Odocoileus virginianus), New York State","volume":"104","year":"2020","journal-title":"Am J Trop Med Hyg"},{"key":"2024111108351623000_2024.11.06.622176v1.7","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268818001000"},{"key":"2024111108351623000_2024.11.06.622176v1.8","doi-asserted-by":"publisher","DOI":"10.4269\/AJTMH.1982.31.1238"},{"key":"2024111108351623000_2024.11.06.622176v1.9","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1984.33.1218"},{"key":"2024111108351623000_2024.11.06.622176v1.10","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7234a1"},{"key":"2024111108351623000_2024.11.06.622176v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.09.001"},{"key":"2024111108351623000_2024.11.06.622176v1.12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2204706119"},{"key":"2024111108351623000_2024.11.06.622176v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48989-5"},{"key":"2024111108351623000_2024.11.06.622176v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-023-00917-w"},{"key":"2024111108351623000_2024.11.06.622176v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-024-01672-3"},{"key":"2024111108351623000_2024.11.06.622176v1.16","doi-asserted-by":"crossref","unstructured":"Devignot S , Sha TW , Burkard TR , Schmerer P , Hagelkruys A , Mirazimi A , Elling U , Penninger JM , Weber F. 2023. 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