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Sequence and phylogenetic analyses of the complete 1918 haemagglutinin (HA) and neuraminidase (NA) genes show them to be the most avian\u2013like of mammalian sequences and support the hypothesis that the pandemic virus contained surface protein\u2013encoding genes derived from an avian influenza strain and that the 1918 virus is very similar to the common ancestor of human and classical swine H1N1 influenza strains. Neither the 1918 HA genes nor the NA genes possessed mutations that are known to increase tissue tropicity, which accounts for the virulence of other influenza strains such as A\/WSN\/33 or fowl plague viruses. The complete sequence of the nonstructural (NS) gene segment of the 1918 virus was deduced and tested for the hypothesis that the enhanced virulence in 1918 could have been due to type I interferon inhibition by the NS1 protein. The results from these experiments were inconclusive. Sequence analysis of the 1918 pandemic influenza virus is allowing us to test hypotheses as to the origin and virulence of this strain. This information should help to elucidate how pandemic influenza strains emerge and what genetic features contribute to their virulence.<\/jats:p>","DOI":"10.1098\/rstb.2001.1020","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T19:57:35Z","timestamp":1027713455000},"page":"1829-1839","source":"Crossref","is-referenced-by-count":148,"title":["Integrating historical, clinical and molecular genetic data in order to explain the origin and virulence of the 1918 Spanish influenza virus"],"prefix":"10.1098","volume":"356","author":[{"given":"Jeffery K.","family":"Taubenberger","sequence":"first","affiliation":[{"name":"Department of Cellular Pathology and Genetics, Armed Forces Institute of Pathology, Room 1057D, Building 101, 1413 Research Boulevard, Rockville, MD 20850-3125, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann H.","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology and Genetics, Armed Forces Institute of Pathology, Room 1057D, Building 101, 1413 Research Boulevard, Rockville, MD 20850-3125, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Janczewski","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology and Genetics, Armed Forces Institute of Pathology, Room 1057D, Building 101, 1413 Research Boulevard, Rockville, MD 20850-3125, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Fanning","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology and Genetics, Armed Forces Institute of Pathology, Room 1057D, Building 101, 1413 Research Boulevard, Rockville, MD 20850-3125, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2001,12,29]]},"reference":[{"key":"p_1","doi-asserted-by":"crossref","unstructured":"Basler C. 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