Reconstructed 1918 Influenza Virus Induces Immune Response that Fails to Protect

An analysis of mice infected with the reconstructed 1918 influenza virus has revealed that although the infection triggered a very strong immune system response, the response failed to protect the animals from severe lung disease and death. The study which was published by Mount Sinai researchers, working in collaboration with scientists from the University of Washington School of Medicine in Seattle, the Centers for Disease Control and Prevention (CDC), and the Armed Forces Institute of Pathology, appeared in the online edition of Nature on September 27.

This study gives scientists new insight into how highly pathogenic influenza viruses, such as the 1918 Spanish flu, cause disease, says Christopher F. Basler, PhD, assistant professor of microbiology, who collaborated with Peter Palese, PhD, the Horace W. Goldsmith professor and chair of microbiology, and also professor of medicine and Adolfo Garcia-Sastre, PhD, professor of microbiology.

Members of the research team, many of whom had collaborated on the reconstruction of the 1918 influenza virus, wanted to know why the virus, which killed 20 to 40 million people, was so lethal. In the study, researchers infected one group of mice with the reconstructed 1918 influenza virus and a second group with benign human influenza. The mice infected with the 1918 virus showed a rapid and potent immune system response, yet the animals also developed severe lung disease and died. The animals infected with the more benign viruses did not develop an immune response that was as strong, and fewer of these animals died. Genes were expressed from lung tissue samples taken from the mice, enabling the researchers to trace the immune response to each of the infections.

The potent immune system reaction of the mice infected with the 1918 virus is one of the main questions raised by the study, according to Basler. Did the very strong immune system response contribute to their death or was the immune system too overwhelmed to fight the infection?

When the body responds to infection, there are components of the immune system that can be beneficial and those that can be harmful, Basler says. Our next step is to repeat these experiments, but deconstruct what the immune system is doing so that we can understand why it is reacting so strongly, yet failing to fight the infection. By understanding the trajectory of this particular infection, we may also gain insight into how to treat other types of viral infections that are a threat to public health. This could help us develop more targeted therapies to combat pathogenic infections, including different types of influenzas or perhaps avian influenza.