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UW researchers link deadliness of 1918 flu to severe immune system response

University of Washington

The H1N1 influenza strain that caused the 1918 flu pandemic causes a severe immune-system response that likely is what makes the virus so deadly to a host animal or person, according to a new study appearing in the Oct. 5 issue of the journal Nature. The research counters the conventional wisdom on the 1918 flu - that a secondary infection from another virus helped make the pandemic one of the deadliest in the modern era.

Researchers at the University of Washington and other institutions studied the response of lung cells in mice infected with the virus. They conducted a functional genomic analysis of those cells to monitor which genes were activated during the course of an infection. Researchers found that several genes related to immune responses were activated, as were genes related to programmed cell death, which occurs when the body kills off infected cells to stave off an infection.

"What we think is happening is that the host's inflammatory response is being highly activated by the virus, and that response is making the virus much more damaging to the host," explained Dr. John Kash, research assistant professor of microbiology at the UW and lead author of the study. "The host's immune system may be overreacting and killing off too many cells, and that may be a key contributor to what makes this virus more pathogenic."

The 1918 flu pandemic, also known as the Spanish Flu, spread across the world in 1918 and 1919, and killed an estimated 25 million to 50 million people or more worldwide. Unlike seasonal flu, which typically hits children, the elderly and people with compromised immune systems the hardest, the 1918 flu affected many younger adults and people without immune-system problems. Modern researchers have long wondered why that influenza strain was so deadly, and why it affected many people outside the populations normally hard-hit by the flu.

One theory that scientists have had on the 1918 flu pandemic was that a secondary infection followed closely on the heels of the main influenza virus, striking people while their immune system was compromised from the flu. This new research indicates that there is something particular about the 1918 influenza strain that makes it especially deadly.

The findings also show Kash and his colleagues an opening in learning how to fight pandemic influenza. If the host's own overzealous immune-system response is partly to blame for the strong effects of the flu strain, then researchers may be able to treat the virus by targeting the host's immune system.

"We're trying to find targets in the host, instead of just in the virus itself," said Dr. Michael Katze, professor of microbiology at the UW, who led the research group. "Then you could have a one-two punch that affects the viral infection, but also dampens the host immune-system response."


The study also included researchers at the Centers for Disease Control and Prevention, in Atlanta; the Department of Microbiology at the Mount Sinai School of Medicine, in New York; the Armed Forces Institute of Pathology, in Rockville, Md.; and the Agricultural Research Laboratory of the U.S. Department of Agriculture, in Athens, Ga. The study was funded by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, and the National Institute on Drug Abuse, all part of the National Institutes of Health.

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