Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus

The 'Spanish' influenza pandemic of 1918-19 was the most devastating outbreak of infectious disease in recorded history. At least 20 million people died from their illness, which was characterized by an unusually severe and rapid clinical course. The complete sequencing of several genes of...

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Bibliographic Details
Published in:Nature 2004-10, Vol.431 (7009), p.703-707
Main Authors: Kawaoka, Yoshihiro, Kobasa, Darwyn, Takada, Ayato, Shinya, Kyoko, Hatta, Masato, Halfmann, Peter, Theriault, Steven, Suzuki, Hiroshi, Nishimura, Hidekazu, Mitamura, Keiko, Sugaya, Norio, Usui, Taichi, Murata, Takeomi, Maeda, Yasuko, Watanabe, Shinji, Suresh, M, Suzuki, Takashi, Suzuki, Yasuo, Feldmann, Heinz
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Animals
Antibodies, Viral - immunology
Binding, Competitive
Cell Line
Child
Child, Preschool
Dogs
Genes
Genes, Viral - genetics
Genetic Engineering
Genetic research
Glycoproteins
Health aspects
Hemagglutinin Glycoproteins, Influenza Virus - genetics
Hemagglutinin Glycoproteins, Influenza Virus - immunology
Hemagglutinin Glycoproteins, Influenza Virus - metabolism
Hemorrhage - complications
Hemorrhage - pathology
Hemorrhage - virology
Humans
Immune Sera - immunology
Infant
Influenza
Influenza A virus
Influenza A virus - genetics
Influenza A virus - immunology
Influenza A virus - pathogenicity
Influenza viruses
Influenza, Human - complications
Influenza, Human - epidemiology
Influenza, Human - pathology
Influenza, Human - virology
Lung - pathology
Lung - virology
Mice
Microbiological research
Middle Aged
Neuraminidase - genetics
Neuraminidase - immunology
Neuraminidase - metabolism
Neutralization Tests
Pandemics
Physiological aspects
Proteins
Recombination, Genetic - genetics
Time Factors
Virulence (Microbiology)
Virulence - genetics
Virulence Factors - genetics
Virulence Factors - metabolism
Viruses
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Summary:The 'Spanish' influenza pandemic of 1918-19 was the most devastating outbreak of infectious disease in recorded history. At least 20 million people died from their illness, which was characterized by an unusually severe and rapid clinical course. The complete sequencing of several genes of the 1918 influenza virus has made it possible to study the functions of the proteins encoded by these genes in viruses generated by reverse genetics, a technique that permits the generation of infectious viruses entirely from cloned complementary DNA. Thus, to identify properties of the 1918 pandemic influenza A strain that might be related to its extraordinary virulence, viruses were produced containing the viral haemagglutinin (HA) and neuraminidase (NA) genes of the 1918 strain. The HA of this strain supports the pathogenicity of a mouse-adapted virus in this animal. Here we demonstrate that the HA of the 1918 virus confers enhanced pathogenicity in mice to recent human viruses that are otherwise non-pathogenic in this host. Moreover, these highly virulent recombinant viruses expressing the 1918 viral HA could infect the entire lung and induce high levels of macrophage-derived chemokines and cytokines, which resulted in infiltration of inflammatory cells and severe haemorrhage, hallmarks of the illness produced during the original pandemic.
ISSN:0028-0836
1476-4687
DOI:10.1038/nature02951