1918 flu - REPORTS Initial Genetic Characterization of the...

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Initial Genetic Characterization of the 1918 “Spanish” Influenza Virus Jeffery K. Taubenberger,* ² Ann H. Reid, ² Amy E. Krafft, Karen E. Bijwaard, Thomas G. Fanning The “Spanish” influenza pandemic killed at least 20 million people in 1918–1919, making it the worst infectious pandemic in history. Understanding the origins of the 1918 virus and the basis for its exceptional virulence may aid in the prediction of future influenza pandemics. RNA from a victim of the 1918 pandemic was isolated from a formalin-fixed, paraffin-embedded, lung tissue sample. Nine fragments of viral RNA were sequenced from the coding regions of hemagglutinin, neuraminidase, nucleoprotein, matrix protein 1, and matrix protein 2. The sequences are consistent with a novel H1N1 influenza A virus that belongs to the subgroup of strains that infect humans and swine, not the avian subgroup. T he influenza pandemic of 1918 was ex - ceptional in both breadth and depth. Out - breaks of the disease swept not only North America and Europe but spread as far as the Alaskan wilderness and the most remote islands of the Pacific. Large proportions of the population became ill; 28% of the U.S. population is estimated to have been infect - ed ( 1 ). The disease was also exceptionally severe, with mortality rates among the in - fected of over 2.5%, as compared with less than 0.1% in other influenza epidemics ( 2 , 3 ). Furthermore, in the 1918 pandemic, most deaths occurred among young adults, a group that usually has a very low death rate from influenza. Influenza and pneumonia death rates for 15 - to 34 - year - olds were more than 20 times higher in 1918 than in previous years ( 4 ). It has been estimated that the influenza epidemic of 1918 killed 675,000 Americans, including 43,000 ser - vicemen mobilized for World War I ( 5 ). The impact was so profound as to depress the average life expectancy in the United States by more than 10 years ( 6 ). The unusual severity of the 1918 pan - demic and the exceptionally high mortality it caused among young adults have stimu - lated great interest in the influenza strain responsible for the 1918 outbreak. Charac - terization of this virus may help to elucidate the mechanisms whereby novel influenza viruses evolve and circulate in humans. Be - cause the first human influenza viruses were not isolated until the early 1930s ( 7 , 8 ), characterization of the 1918 strain has had to rely on indirect evidence. The natural reservoir for influenza virus is thought to be wild waterfowl. Periodically, genetic mate - rial from avian strains emerges in strains infectious to humans. Because pigs can be infected with both avian and human strains, they are thought to be an interme - diary in this process. Influenza strains with recently acquired genetic material are re - sponsible for pandemic influenza outbreaks ( 9 ). Analysis of survivor antibody titers from the late 1930s and historical projec - tion of phylogenetic analyses suggest that the 1918 strain was an H1N1
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1918 flu - REPORTS Initial Genetic Characterization of the...

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