Your genes may hold key to how sick you get from the flu

With lessons from the 1918 flu pandemic in the rearview mirror and the avian flu a looming obstacle in the road ahead, researchers from Southern Illinois University School of Medicine are trying to understand why a flu virus kills some people but not others.

With the help of some high tech equipment, well-defined mouse models and lots of analytical know how, physiologists are beginning to hone in on the secret to this differential response. It's probably in the genes - and the proteins they encode.

Two studies to be presented at The American Physiological Society conference "Physiological Genomics and Proteomics of Lung Disease" have found that a strain of mice that is more likely to die of influenza infection mounts a dramatically enhanced immune response in the lungs compared to a strain of mice that generally develops milder disease.

The long-term goal of these studies is to identify genes that control the individual variation in inflammation during influenza infection. This information could ultimately help identify those most at risk to develop severe disease and die from the flu, and help doctors direct vaccines, anti-viral and anti-inflammatory medications to those who need them most.

The researchers will present the study "Inflammatory responses in inbred mice with different susceptibility phenotypes to Influenza A virus infection," on Nov. 3. The study was carried out by Rita Trammell and Linda Toth of the Southern Illinois University School of Medicine, Springfield, Ill. The conference takes place Nov. 2-5 in Fort Lauderdale.

Lessons from 1918

"Flu epidemics typically kill the very old and the very young. But the 1918 epidemic killed millions around the world, including many healthy young adults. The healthy immune systems of young adults produced an overly strong immune response that resulted in severe inflammation of the lungs. Similar to the 1918 pandemic virus, most H5N1 avian influenza virus infections occur in young adults with no pre-existing medical conditions," Trammell noted.

"The recent emergence of the highly pathogenic H5N1 influenza virus has raised international concerns that continued evolution of the virus could cause a pandemic with global health and economic consequences," Trammell said. "Should this occur, the ability to identify those at highest risk for developing severe disease may help to determine who would benefit most if vaccines and anti-viral therapeutics are in limited supply," she said.

"Studies to date have focused on the virus itself to determine what makes some viruses killers," she said. "Our research looks at the role of the host's genetic background, an area that has remained largely unexplored."

Flu fells some, not others

Trammell and Toth infected two strains of laboratory mice with an Influenza A virus. "Our previous studies established that if you give the same dose of influenza A virus to both strains of mice, about half of the BALB/cByJ (Type B) mice will die, compared to about 10% of the C57BL/6J (Type C) mice," Trammell said.