{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T01:15:54Z","timestamp":1784855754981,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009356","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T00:00:00Z","timestamp":1615420800000}}],"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JSPS Postdoctoral Fellowship for Research Abroad (H28-803)"],"award-info":[{"award-number":["JSPS Postdoctoral Fellowship for Research Abroad (H28-803)"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JSPS Postdoctoral Fellowship for Research Abroad (H29-296)"],"award-info":[{"award-number":["JSPS Postdoctoral Fellowship for Research Abroad (H29-296)"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","award":["Burroughs Wellcome Fund Career Award for Medical Scientists (2016)"],"award-info":[{"award-number":["Burroughs Wellcome Fund Career Award for Medical Scientists (2016)"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Several arenaviruses cause hemorrhagic fevers in humans with high case fatality rates. A vaccine named Candid#1 is available only against Junin virus (JUNV) in Argentina. Specific N-linked glycans on the arenavirus surface glycoprotein (GP) mask important epitopes and help the virus evade antibody responses. However the role of GPC glycans in arenavirus pathogenicity is largely unclear. In a lethal animal model of hemorrhagic fever-causing Machupo virus (MACV) infection, we found that a chimeric MACV with the ectodomain of GPC from Candid#1 vaccine was partially attenuated. Interestingly, mutations resulting in acquisition of N-linked glycans at GPC N83 and N166 frequently occurred in late stages of the infection. These glycosylation sites are conserved in the GPC of wild-type MACV, indicating that this is a phenotypic reversion for the chimeric MACV to gain those glycans crucial for infection <jats:italic>in vivo<\/jats:italic>. Further studies indicated that the GPC mutant viruses with additional glycans became more resistant to neutralizing antibodies and more virulent in animals. On the other hand, disruption of these glycosylation sites on wild-type MACV GPC rendered the virus substantially attenuated <jats:italic>in vivo<\/jats:italic> and also more susceptible to antibody neutralization, while loss of these glycans did not affect virus growth in cultured cells. We also found that MACV lacking specific GPC glycans elicited higher levels of neutralizing antibodies against wild-type MACV. Our findings revealed the critical role of specific glycans on GPC in arenavirus pathogenicity and have important implications for rational design of vaccines against this group of hemorrhagic fever-causing viruses.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009356","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T18:34:48Z","timestamp":1614623688000},"page":"e1009356","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["Glycoprotein N-linked glycans play a critical role in arenavirus 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Albarino","year":"2011","journal-title":"Journal of virology"},{"key":"ppat.1009356.ref032","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3389\/fcimb.2017.00020","article-title":"Absence of an N-Linked Glycosylation Motif in the Glycoprotein of the Live-Attenuated Argentine Hemorrhagic Fever Vaccine, Candid #1, Results in Its Improper Processing, and Reduced Surface Expression.","volume":"7","author":"JT Manning","year":"2017","journal-title":"Frontiers in cellular and infection microbiology."},{"issue":"8","key":"ppat.1009356.ref033","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.01693-19","article-title":"The Glycoprotein of the Live-Attenuated Junin Virus Vaccine Strain Induces Endoplasmic Reticulum Stress and Forms Aggregates prior to Degradation in the Lysosome","volume":"94","author":"JT Manning","year":"2020","journal-title":"Journal of 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Marzi","year":"2006"},{"key":"ppat.1009356.ref052","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1186\/1743-422X-10-221","article-title":"Vascular leak ensues a vigorous proinflammatory cytokine response to Tacaribe arenavirus infection in AG129 mice.","volume":"10","author":"EJ Sefing","year":"2013","journal-title":"Virology journal."},{"issue":"1","key":"ppat.1009356.ref053","doi-asserted-by":"crossref","first-page":"4679","DOI":"10.1038\/s41598-017-04889-x","article-title":"An attenuated Machupo virus with a disrupted L-segment intergenic region protects guinea pigs against lethal Guanarito virus infection.","volume":"7","author":"JW Golden","year":"2017","journal-title":"Scientific reports."},{"issue":"4","key":"ppat.1009356.ref054","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1128\/JVI.02925-13","article-title":"Rescue of a recombinant Machupo virus from cloned cDNAs and in vivo characterization in interferon (alphabeta\/gamma) receptor double knockout 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