{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T19:59:25Z","timestamp":1772135965271,"version":"3.50.1"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,6,13]],"date-time":"2017-06-13T00:00:00Z","timestamp":1497312000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,6,13]],"date-time":"2017-06-13T00:00:00Z","timestamp":1497312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Marburg virus (MARV) has caused outbreaks of filoviral hemorrhagic fever since its discovery in 1967. The largest and deadliest outbreak occurred in Angola in 2005, with 252 cases and 227 deaths. In 2014, we developed a mouse-adapted MARV, Angola variant through serial passaging in mice. The mouse-adapted MARV exhibits many of the hallmarks of MARV disease in humans. By applying deep-sequencing to every passage of the virus, we are able to study virus evolution in this host with surprising precision. We show that two regions go through substantial changes: the intergenic region between NP and VP35, as well as the first 100 amino acids of the VP40 protein. Our results also reveal that there were profound changes during the production of the final virus stock in cell culture. Overall, our results show that a handful of regions carry most of the mutations acquired during the adaptation of the virus to a new host and that many mutations become fixed very early during the adaptation process.<\/jats:p>","DOI":"10.1038\/s41598-017-03318-3","type":"journal-article","created":{"date-parts":[[2017,6,7]],"date-time":"2017-06-07T07:55:14Z","timestamp":1496822114000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Deep-sequencing of Marburg virus genome during sequential mouse passaging and cell-culture adaptation reveals extensive changes over time"],"prefix":"10.1038","volume":"7","author":[{"given":"Haiyan","family":"Wei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Audet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shihua","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueyong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd","family":"Cutts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Theriault","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianli","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Kobinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangguo","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,6,13]]},"reference":[{"key":"3318_CR1","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1007\/s00705-012-1594-2","volume":"158","author":"JH Kuhn","year":"2013","unstructured":"Kuhn, J. H. et al. Virus nomenclature below the species level: a standardized nomenclature for laboratory animal-adapted strains and variants of viruses assigned to the family Filoviridae. Arch. Virol. \n                           158, 1425\u201332 (2013).","journal-title":"Arch. Virol."},{"key":"3318_CR2","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1111\/j.1469-0691.2011.03535.x","volume":"17","author":"EM Leroy","year":"2011","unstructured":"Leroy, E. M., Gonzalez, J. & Baize, S. Ebola and Marburg haemorrhagic fever viruses: major scientific advances, but a relatively minor public health threat for Africa. Clin. Microbiol. Infect. \n                           17, 964\u201376 (2011).","journal-title":"Clin. Microbiol. Infect."},{"key":"3318_CR3","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1136\/bmj.4.5995.489","volume":"4","author":"JS Gear","year":"1975","unstructured":"Gear, J. S. et al. Outbreake of Marburg virus disease in Johannesburg. Br. Med. J. \n                           4, 489\u201393 (1975).","journal-title":"Br. Med. J."},{"key":"3318_CR4","unstructured":"World Health Organisation. Marburg haemorrhagic fever in Angola \u2013 update 25. (2005)."},{"key":"3318_CR5","doi-asserted-by":"publisher","first-page":"e1000536","DOI":"10.1371\/journal.ppat.1000536","volume":"5","author":"JS Towner","year":"2009","unstructured":"Towner, J. S. et al. Isolation of genetically diverse Marburg viruses from Egyptian fruit bats. PLoS Pathog. \n                           5, e1000536 (2009).","journal-title":"PLoS Pathog."},{"key":"3318_CR6","doi-asserted-by":"publisher","first-page":"12703","DOI":"10.1128\/JVI.01643-14","volume":"88","author":"X Qiu","year":"2014","unstructured":"Qiu, X. et al. Establishment and Characterization of a Lethal Mouse Model for the Angola Strain of Marburg Virus. J. Virol. \n                           88, 12703\u201312714 (2014).","journal-title":"J. Virol."},{"key":"3318_CR7","doi-asserted-by":"publisher","first-page":"3566","DOI":"10.1128\/JVI.74.8.3566-3571.2000","volume":"74","author":"R Miralles","year":"2000","unstructured":"Miralles, R., Moya, A. & Elena, S. F. Diminishing Returns of Population Size in the Rate of RNA Virus Adaptation. J. Virol. \n                           74, 3566\u20133571 (2000).","journal-title":"J. Virol."},{"key":"3318_CR8","doi-asserted-by":"publisher","first-page":"4309","DOI":"10.1128\/JVI.02575-10","volume":"85","author":"C Valmas","year":"2011","unstructured":"Valmas, C. & Basler, C. F. Marburg virus VP40 antagonizes interferon signaling in a species-specific manner. J. Virol. \n                           85, 4309\u201317 (2011).","journal-title":"J. Virol."},{"key":"3318_CR9","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1128\/JVI.01597-15","volume":"90","author":"S-I Oda","year":"2016","unstructured":"Oda, S.-I. et al. Crystal Structure of Marburg Virus VP40 Reveals a Broad, Basic Patch for Matrix Assembly and a Requirement of the N-Terminal Domain for Immunosuppression. J. Virol. \n                           90, 1839\u201348 (2016).","journal-title":"J. Virol."},{"key":"3318_CR10","doi-asserted-by":"publisher","first-page":"S219","DOI":"10.1093\/infdis\/jiv010","volume":"212","author":"AR Feagins","year":"2015","unstructured":"Feagins, A. R. & Basler, C. F. Amino Acid Residue at Position 79 of Marburg Virus VP40 Confers Interferon Antagonism in Mouse Cells. J. Infect. Dis. \n                           212, S219\u2013S225 (2015).","journal-title":"J. Infect. Dis."},{"key":"3318_CR11","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1128\/JVI.02670-15","volume":"90","author":"A Koehler","year":"2016","unstructured":"Koehler, A. et al. A Single Amino Acid Change in the Marburg Virus Matrix Protein VP40 Provides a Replicative Advantage in a Species-Specific Manner. J. 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