Abstract
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.
Publication types
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Historical Article
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Bronchi / virology
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Cell Line
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Chick Embryo / virology
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Female
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Genes, Viral*
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Genetic Techniques
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Hemagglutinin Glycoproteins, Influenza Virus / genetics
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Hemagglutinin Glycoproteins, Influenza Virus / metabolism
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History, 20th Century
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Humans
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Influenza A Virus, H1N1 Subtype / genetics*
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Influenza A Virus, H1N1 Subtype / pathogenicity*
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Influenza A Virus, H1N1 Subtype / physiology
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Influenza, Human / epidemiology
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Influenza, Human / history
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Influenza, Human / virology*
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Lung / pathology
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Lung / virology
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Mice
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Mice, Inbred BALB C
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Neuraminidase / genetics
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Neuraminidase / metabolism
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Orthomyxoviridae Infections / pathology
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Orthomyxoviridae Infections / virology*
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RNA, Viral / genetics
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Recombination, Genetic
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Respiratory Mucosa / virology
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Trypsin / metabolism
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Viral Plaque Assay
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Virulence / genetics
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Virus Replication
Substances
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Hemagglutinin Glycoproteins, Influenza Virus
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RNA, Viral
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Neuraminidase
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Trypsin