Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus

• Published in: Science (American Association for the Advancement of Science) Vol. 310; no. 5745; pp. 77 - 80
• Main Authors: Tumpey, Terrence M, Basler, Christopher F, Aguilar, Patricia V, Zeng, Hui, Solórzano, Alicia, Swayne, David E, Cox, Nancy J, Katz, Jacqueline M, Taubenberger, Jeffery K, Palese, Peter, García-Sastre, Adolfo
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 07-10-2005; The American Association for the Advancement of Science
• Subjects: 1918 Spanish influenza pandemic virus; Analysis; Animals; Biological and medical sciences; Body Weight; bronchi; Bronchi - virology; Cell Line; Chick Embryo - virology; Chicken eggs; Coding; Disease control; Disease transmission; eggs; Epithelial cells; epithelium; Female; Fundamental and applied biological sciences. Psychology; genes; Genes, Viral; Genetic Techniques; Genetics; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - metabolism; History, 20th Century; human cell lines; Humans; Infections; Influenza; Influenza A virus; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - pathogenicity; Influenza A Virus, H1N1 Subtype - physiology; Influenza viruses; Influenza, Human - epidemiology; Influenza, Human - history; Influenza, Human - virology; Lung - pathology; Lung - virology; Lungs; Mice; Mice, Inbred BALB C; microbial growth; Microbiology; molecular genetics; mortality; Mortality Rate; Neuraminidase - genetics; Neuraminidase - metabolism; Orthomyxoviridae; Orthomyxoviridae Infections - pathology; Orthomyxoviridae Infections - virology; Pandemics; Pulmonary alveoli; Recombination, Genetic; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Research Article; Respiratory Mucosa - virology; reverse genetics; RNA, Viral - genetics; Rotation; trypsin; Trypsin - metabolism; viral diseases of animals and humans; Viral Plaque Assay; Virology; Virulence; Virulence - genetics; Virus Replication; Viruses; Infection; Pathogenicity; Phenotype; Gene; Viral disease; Virulence; Influenza A; Spanish flu
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1119392

The pandemic influenza virus of 1918-1919 killed an estimated 20 to 50 million people worldwide. With the recent availability of the complete 1918 influenza virus coding sequence, we used reverse genetics to generate an influenza virus bearing all eight gene segments of the pandemic virus to study the properties associated with its extraordinary virulence. In stark contrast to contemporary human influenza H1N1 viruses, the 1918 pandemic virus had the ability to replicate in the absence of trypsin, caused death in mice and embryonated chicken eggs, and displayed a high-growth phenotype in human bronchial epithelial cells. Moreover, the coordinated expression of the 1918 virus genes most certainly confers the unique high-virulence phenotype observed with this pandemic virus.