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Here, we identified a variant of MACV strain Carvallo termed Car<jats:sup>91<\/jats:sup> that was attenuated in guinea pigs. Infection of guinea pigs with an earlier passage of Carvallo, termed Car<jats:sup>68<\/jats:sup>, resulted in a lethal disease with a 63% mortality rate. Sequencing analysis revealed that compared to Car<jats:sup>68<\/jats:sup>, Car<jats:sup>91<\/jats:sup> had a 35 nucleotide (nt) deletion and a point mutation within the L-segment intergenic region (IGR), and three silent changes in the polymerase gene that did not impact amino acid coding. No changes were found on the S-segment. Because it was apathogenic, we determined if Car<jats:sup>91<\/jats:sup> could protect guinea pigs against Guanarito virus (GTOV), a distantly related NW arenavirus. While na\u00efve animals succumbed to GTOV infection, 88% of the Car<jats:sup>91<\/jats:sup>-exposed guinea pigs were protected. These findings indicate that attenuated MACV vaccines can provide heterologous protection against NW arenaviruses. The disruption in the L-segment IGR, including a single point mutant and 35 nt partial deletion, were the only major variance detected between virulent and avirulent isolates, implicating its role in attenuation. Overall, our data support the development of live-attenuated arenaviruses as broadly protective pan-arenavirus vaccines.<\/jats:p>","DOI":"10.1038\/s41598-017-04889-x","type":"journal-article","created":{"date-parts":[[2017,6,29]],"date-time":"2017-06-29T10:34:15Z","timestamp":1498732455000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["An attenuated Machupo virus with a disrupted L-segment intergenic region protects guinea pigs against lethal Guanarito virus infection"],"prefix":"10.1038","volume":"7","author":[{"given":"Joseph W.","family":"Golden","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett","family":"Beitzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason T.","family":"Ladner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric M.","family":"Mucker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Kwilas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5062-1938","authenticated-orcid":false,"given":"Gustavo","family":"Palacios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4475-0415","authenticated-orcid":false,"given":"Jay W.","family":"Hooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,7,5]]},"reference":[{"key":"4889_CR1","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1128\/jvi.26.2.485-497.1978","volume":"26","author":"AC Vezza","year":"1978","unstructured":"Vezza, A. C. et al. Virion RNA species of the arenaviruses Pichinde, Tacaribe, and Tamiami. J Virol \n                           26, 485\u2013497 (1978).","journal-title":"J Virol"},{"key":"4889_CR2","unstructured":"Buchmeier, M. J., De la Torre, J. C. & Peters, C. J. in Fields Virology Vol. 2 (eds D.M. Knipe & P.M. Howley) 1283\u20131303 (Lippencott, Williams and Wilkins, 2013)."},{"key":"4889_CR3","first-page":"5","volume":"133","author":"DH Bishop","year":"1987","unstructured":"Bishop, D. H. & Auperin, D. D. Arenavirus gene structure and organization. Curr Top Microbiol Immunol \n                           133, 5\u201317 (1987).","journal-title":"Curr Top Microbiol Immunol"},{"key":"4889_CR4","doi-asserted-by":"publisher","first-page":"12978","DOI":"10.1073\/pnas.2133782100","volume":"100","author":"M Perez","year":"2003","unstructured":"Perez, M., Craven, R. C. & de la Torre, J. C. The small RING finger protein Z drives arenavirus budding: implications for antiviral strategies. 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