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Prophylaxis for Argentine Haemorrhagic Fever (AHF), caused by the arenavirus Jun\u00edn (JUNV), has been achieved by the use of a live attenuated vaccine, named Candid#1. The standard treatment of AHF is transfusion of convalescent human plasma. Our aim was to develop an alternative and safer treatment for AHF based on the use of virus-neutralizing single domain antibodies (VHHs). We describe the first reported VHHs directed against an arenavirus. These VHHs could neutralize Candid#1 by altering virion binding\/fusion. Surprisingly, the neutralizing VHHs appeared to be specific for the viral nucleoprotein (N) that is not known to be involved in arenavirus entry. Candid#1 VHH-escape viruses had acquired a predicted N-glycosylation site in the surface glycoprotein GP1 that is present in highly pathogenic JUNV strains. Accordingly, the Candid#1-neutralizing VHHs could not neutralize pathogenic JUNV strains, but they could still bind to cells infected with a pathogenic strain or the escape mutant viruses. These results show that the attenuated strains of JUNV can be potently neutralized by nucleoprotein-specific VHHs.<\/jats:p>","DOI":"10.1038\/s41598-018-29508-1","type":"journal-article","created":{"date-parts":[[2018,7,24]],"date-time":"2018-07-24T11:27:04Z","timestamp":1532431624000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Neutralization of Jun\u00edn virus by single domain antibodies targeted against the nucleoprotein"],"prefix":"10.1038","volume":"8","author":[{"given":"Florencia","family":"Linero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Sep\u00falveda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Christopoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paco","family":"Hulpiau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Scolaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3861-6965","authenticated-orcid":false,"given":"Xavier","family":"Saelens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,7,30]]},"reference":[{"key":"29508_CR1","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1099\/vir.0.051995-0","volume":"94","author":"R Bodewes","year":"2013","unstructured":"Bodewes, R. et al. 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