{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:49:13Z","timestamp":1791222553573,"version":"4.1.0"},"reference-count":83,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2016,2,19]],"date-time":"2016-02-19T00:00:00Z","timestamp":1455840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>West Nile virus (WNV) strains may differ significantly in neuroinvasiveness in vertebrate hosts. In contrast to genetic lineage 1 WNVs, molecular determinants of pathogenic lineage 2 strains have not been experimentally confirmed so far. A full-length infectious clone of a neurovirulent WNV lineage 2 strain (578\/10; Central Europe) was generated and amino acid substitutions that have been shown to attenuate lineage 1 WNVs were introduced into the nonstructural proteins (NS1 (P250L), NS2A (A30P), NS3 (P249H) NS4B (P38G, C102S, E249G)). The mouse neuroinvasive phenotype of each mutant virus was examined following intraperitoneal inoculation of C57BL\/6 mice. Only the NS1-P250L mutation was associated with a significant attenuation of virulence in mice compared to the wild-type. Multiplication kinetics in cell culture revealed significantly lower infectious virus titres for the NS1 mutant compared to the wild-type, as well as significantly lower amounts of positive and negative stranded RNA.<\/jats:p>","DOI":"10.3390\/v8020049","type":"journal-article","created":{"date-parts":[[2016,2,19]],"date-time":"2016-02-19T11:29:39Z","timestamp":1455881379000},"page":"49","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["In Vitro and in Vivo Evaluation of Mutations in the NS Region of Lineage 2 West Nile Virus Associated with Neuroinvasiveness in a Mammalian Model"],"prefix":"10.3390","volume":"8","author":[{"given":"Katalin","family":"Szentp\u00e1li-Gavall\u00e9r","sequence":"first","affiliation":[{"name":"Veterinary Diagnostic Directorate, National Food Chain Safety Office, H-1143, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Lim","sequence":"additional","affiliation":[{"name":"Viroscience Laboratory, Erasmus Medical Centre, 3015CN, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Dencs\u0151","sequence":"additional","affiliation":[{"name":"Veterinary Diagnostic Directorate, National Food Chain Safety Office, H-1143, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kriszti\u00e1n","family":"B\u00e1nyai","sequence":"additional","affiliation":[{"name":"Institute for Veterinary Medical Research, Centre for Agricultural Research, Hungarian Academy of Sciences, H-1143, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penelope","family":"Koraka","sequence":"additional","affiliation":[{"name":"Viroscience Laboratory, Erasmus Medical Centre, 3015CN, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Osterhaus","sequence":"additional","affiliation":[{"name":"Viroscience Laboratory, Erasmus Medical Centre, 3015CN, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron","family":"Martina","sequence":"additional","affiliation":[{"name":"Viroscience Laboratory, Erasmus Medical Centre, 3015CN, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Bakonyi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, Faculty of Veterinary Science, Szent Istv\u00e1n University, H-1143, Budapest, Hungary"},{"name":"Viral Zoonoses, Emerging and Vector-Borne Infections Group, Institute of Virology, University of Veterinary Medicine, A-1210, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1d\u00e1m","family":"B\u00e1lint","sequence":"additional","affiliation":[{"name":"Veterinary Diagnostic Directorate, National Food Chain Safety Office, H-1143, Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/j.1863-2378.2008.01208.x","article-title":"The zoonotic flaviviruses of southern, south-eastern and eastern Asia, and Australasia: the potential for emergent viruses","volume":"56","author":"Mackenzie","year":"2009","journal-title":"Zoonoses Public Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.3201\/eid2012.140921","article-title":"Putative new West Nile virus lineage in Uranotaenia unguiculata mosquitoes, Austria, 2013","volume":"20","author":"Pachler","year":"2014","journal-title":"Emerg. 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