(SALT LAKE CITY)—By analyzing patterns of genetic change in thousands of flu strains, an international group of researchers has identified a previously unknown gene, PA-X, which helps the virus control how the body responds to infection.
The study, published online in Science on Thursday, June 28, 2012, also gives insight into how the virus causes severe infections, and also may help research into influenza treatments. The study examined how PA-X affected the behavior of the virulent Spanish flu, which killed millions of people a 1918 worldwide pandemic.
In studies with mice, the researchers found that when the PA-X gene was active, it reduced the impact of the infection and the recovery rate of mice infected with influenza A virus. But when PA-X did not work properly, it caused the immune system to overreact and made the infection worse.
"Just finding this gene in the first place is important, but the find is even more significant because of the role the gene plays in the body's response to flu," said Paul Digard, a Professor at the Roslin Institute at the University of Edinburgh and lead-corresponding author on the study.
The newly discovered gene is expressed via a non-standard event in the readout of the genetic information into active protein products. It is the nature and mechanism of this non-standard event that was addressed by the University of Utah component of the team. The researchers, who are in the Department of Human Genetics, are Norma Wills and John F. Atkins (who is also a member of the Biosciences Institute at University College Cork, Ireland). Michael T. Howard, Ph.D.,research associate professor of human genetics, provided an invaluable ingredient for the work and Chad Nelson, Ph.D.,research assistant professor of medicinal chemistry at the College of Pharmacy and director of the mass spectrometry and proteomics core facility at the U of U, performed essential follow-up work.
Long-standing collaborations and support from Raymond F. Gesteland, U of U emeritus professor of human genetics, and Robert B. Weiss, professor of human genetics, provided the environment that allowed the Utah component of the work to occur.
Other institutions involved in the study are Cambridge University, United Kingdom; National Institute of Allergy and Infectious Disease (National Institutes of Health), Bethesda, Md.; and the Institute for Systems Biology, Seattle.