Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science 310:77–80

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. The influenza pandemic of 1918 was excep-tional, resulting in the deaths of up to 50 mil-lion people worldwide, including an estimated 675,000 deaths in the United States (1, 2)