1918 pandemic flu virus ravaged the immune system, study reveals

The Spanish flu virus that killed about 50 million people worldwide in 1918, has just proven that it as lethal as ever.

In a Canadian biohazard laboratory, a reconstructed H1N1 virus was found to easily infect macaque monkeys, spread quickly throughout the lungs, and kill within a few days.

Yoshihiro Kawaoka and his team of scientists compared the effects of the engineered 1918 with a contemporary version of H1N1 on 10 nonhuman primate models (macaques). Within a day to one week of injection, monkeys that were infected with the 1918 virus progressively showed acute respiratory distress. Autopsies showed that the virus had replicated to very high levels and spread rapidly through the respiratory tract, causing severe lung bleeding and injury. In contrast, monkeys infected with the modern H1N1 had very mild, clinical signs and very few of the virus was found in only a small area of the lungs.

In an immune response, cytokines provide the body’s first line of defense by activating further responses and recruiting other immune cells to the sites of infection. Further investigation of the monkeys’ immune system revealed that certain types of cytokines increased to such proportions and became so overstimulated that they turned against their own host (the body) and attacked it. The virus also prevented the production of antiviral immune proteins, hence effectively blocking the body’s ability to stage a counter-attack.

It seemed that the pandemic 1918 virus had some genetic means of triggering an over-reactive immune and inflammatory response that contributed to severe lung tissue damage, disease and death.

These conclusions explain why, unlike contemporary influenza strains that target the very young and eldery, the 1918 pandemic was especially fatal in young adults – they have the more robust immune systems.

The importance of this study points back to global concerns about an H5N1 avian flu pandemic. Characterizing highly pathogenic forms of flu viruses, and understanding our body’s immune responses against them, will aid in development of interventions and treatments against similar threats to our existence.

The international team of scientists who performed the experimens were led by Dr. Yoshihiro Kawaoka. The paper is published in the January issue of Nature.

Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus. Nature 2007. 445:319-323
Fatal immunity and the 1918 virus. Nature 2007. 445: 267-268.
Q&A: The flu pandemic of 1918
Finally, a vaccine against the Spanish flu

Tags: H1N1, Spanish flu, 1918 virus, influenza, macaques, monkeys, immune response, immunity