{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T11:09:37Z","timestamp":1783768177801,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010625","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000}}],"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T00:00:00Z","timestamp":1660521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI053668"],"award-info":[{"award-number":["R01 AI053668"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Lassa virus (LASV) cell entry is mediated by the interaction of the virus glycoprotein complex (GPC) with alpha-dystroglycan at the cell surface followed by binding to LAMP1 in late endosomes. However, LAMP1 is not absolutely required for LASV fusion, as this virus can infect LAMP1-deficient cells. Here, we used LASV GPC pseudoviruses, LASV virus-like particles and recombinant lymphocytic choriomeningitis virus expressing LASV GPC to investigate the role of human LAMP1 (hLAMP1) in LASV fusion with human and avian cells expressing a LAMP1 ortholog that does not support LASV entry. We employed a combination of single virus imaging and virus population-based fusion and infectivity assays to dissect the hLAMP1 requirement for initiation and completion of LASV fusion that culminates in the release of viral ribonucleoprotein into the cytoplasm. Unexpectedly, ectopic expression of hLAMP1 accelerated the kinetics of small fusion pore formation, but only modestly increased productive LASV fusion and infection of human and avian cells. To assess the effects of hLAMP1 in the absence of requisite endosomal host factors, we forced LASV fusion with the plasma membrane by applying low pH. Unlike the conventional LASV entry pathway, ectopic hLAMP1 expression dramatically promoted the initial and full dilation of pores formed through forced fusion at the plasma membrane. We further show that, while the soluble hLAMP1 ectodomain accelerates the kinetics of nascent pore formation, it fails to promote efficient pore dilation, suggesting the hLAMP1 transmembrane domain is involved in this late stage of LASV fusion. These findings reveal a previously unappreciated role of hLAMP1 in promoting dilation of LASV fusion pores, which is difficult to ascertain for endosomal fusion where several co-factors, such as bis(monoacylglycero)phosphate, likely regulate LASV entry.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010625","type":"journal-article","created":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T13:42:42Z","timestamp":1660570962000},"page":"e1010625","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Human LAMP1 accelerates Lassa virus fusion and potently promotes fusion pore dilation upon forcing viral fusion with non-endosomal membrane"],"prefix":"10.1371","volume":"18","author":[{"given":"You","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Carlos de la Torre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5385-3013","authenticated-orcid":true,"given":"Gregory B.","family":"Melikyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,8,15]]},"reference":[{"issue":"7","key":"ppat.1010625.ref001","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.tim.2015.04.006","article-title":"Emerging intracellular receptors for hemorrhagic fever viruses","volume":"23","author":"LT Jae","year":"2015","journal-title":"Trends Microbiol"},{"issue":"1","key":"ppat.1010625.ref002","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3390\/v4010083","article-title":"The curious case of arenavirus entry, and its inhibition","volume":"4","author":"JH Nunberg","year":"2012","journal-title":"Viruses"},{"issue":"11","key":"ppat.1010625.ref003","doi-asserted-by":"crossref","first-page":"5189","DOI":"10.1128\/JVI.00208-06","article-title":"Role of the stable signal peptide and cytoplasmic domain of G2 in regulating intracellular transport of the Junin virus envelope glycoprotein complex","volume":"80","author":"SS Agnihothram","year":"2006","journal-title":"J Virol"},{"issue":"11","key":"ppat.1010625.ref004","doi-asserted-by":"crossref","first-page":"6138","DOI":"10.1128\/JVI.07241-11","article-title":"Dissection of the role of the stable signal peptide of the arenavirus envelope glycoprotein in membrane fusion","volume":"86","author":"EL Messina","year":"2012","journal-title":"J Virol"},{"issue":"15","key":"ppat.1010625.ref005","doi-asserted-by":"crossref","first-page":"7775","DOI":"10.1128\/JVI.00642-06","article-title":"Role of the stable signal peptide of Junin arenavirus envelope glycoprotein in pH-dependent membrane fusion","volume":"80","author":"J York","year":"2006","journal-title":"J Virol"},{"issue":"9","key":"ppat.1010625.ref006","doi-asserted-by":"crossref","first-page":"4121","DOI":"10.1128\/JVI.02410-08","article-title":"Intersubunit interactions modulate pH-induced activation of membrane fusion by the Junin virus envelope glycoprotein GPC","volume":"83","author":"J York","year":"2009","journal-title":"J Virol"},{"issue":"18","key":"ppat.1010625.ref007","doi-asserted-by":"crossref","first-page":"8341","DOI":"10.1128\/JVI.01124-16","article-title":"Myristoylation of the Arenavirus Envelope Glycoprotein Stable Signal Peptide Is Critical for Membrane Fusion but Dispensable for Virion Morphogenesis","volume":"90","author":"J York","year":"2016","journal-title":"J Virol"},{"issue":"19","key":"ppat.1010625.ref008","doi-asserted-by":"crossref","first-page":"10783","DOI":"10.1128\/JVI.78.19.10783-10792.2004","article-title":"The signal peptide of the Junin arenavirus envelope glycoprotein is myristoylated and forms an essential subunit of the mature G1-G2 complex","volume":"78","author":"J York","year":"2004","journal-title":"J Virol"},{"issue":"6191","key":"ppat.1010625.ref009","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1126\/science.1252480","article-title":"Virus entry. Lassa virus entry requires a trigger-induced receptor switch","volume":"344","author":"LT Jae","year":"2014","journal-title":"Science"},{"issue":"1","key":"ppat.1010625.ref010","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01818-17","article-title":"Lamp1 Increases the Efficiency of Lassa Virus Infection by Promoting Fusion in Less Acidic Endosomal Compartments","volume":"9","author":"CE Hulseberg","year":"2018","journal-title":"mBio"},{"issue":"22","key":"ppat.1010625.ref011","doi-asserted-by":"crossref","first-page":"10329","DOI":"10.1128\/JVI.01624-16","article-title":"Role of LAMP1 Binding and pH Sensing by the Spike Complex of Lassa Virus","volume":"90","author":"H Cohen-Dvashi","year":"2016","journal-title":"J Virol"},{"issue":"9","key":"ppat.1010625.ref012","doi-asserted-by":"crossref","first-page":"e1009488","DOI":"10.1371\/journal.ppat.1009488","article-title":"The late endosome-resident lipid bis(monoacylglycero)phosphate is a cofactor for Lassa virus 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P.J.","family":"Whelan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,8,15]]},"references-count":33,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1010625","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.06.01.494281","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,15]]}}}