Analysis and Reconstruction of the 1918 Pandemic Flu Virus

Journal Watch. 2005;4(10) 

Summary and Comment

The 1918 influenza pandemic killed 20–50 million people worldwide, including many healthy young adults. A team from the Armed Forces Institute of Pathology (AFIP) extracted viral RNA from autopsy specimens of victims and sequenced the viral genes. As experts have long speculated, the 1918 virus was a true avian flu virus that adapted to humans. In contrast, the 1957 and 1968 flu pandemics involved viruses that evolved from recombination of avian and human viral sequences. The 1918 virus contains several amino acid changes that also are present in the current highly pathogenic H5N1 avian virus that has killed humans in the past 8 years.

Based on the AFIP data, a team at the CDC recreated the 1918 virus and tested it in mice for pathogenicity. Compared with contemporary human flu viruses, the 1918 virus produced nearly 40,000 times more viral particles in lung tissue. It caused severe bronchiolitis and alveolitis, pulmonary edema, and alveolar hemorrhage — just as it had in human lungs in 1918. By creating variants of the virus, with changes in specific genes, the team showed that the hemagglutinin (HA) gene was essential for virulence and that the polymerase genes also made important contributions. Cleavage of the HA protein, a step critical to pathogenesis, occurred by a novel mechanism.

By demonstrating parallels between the 1918 flu virus and the current H5N1 avian virus, these studies increase concern about the potential effect of another global flu pandemic. At the same time, this new knowledge, and the ability to test the pathogenicity of different experimentally created viral mutants, will help us identify targets for treatment and vaccination.

— Anthony L. Komaroff, MD

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