Researchers at Seattle BioMed, together with collaborators at the University of California, San Diego School of Medicine, St. Jude Children’s Research Hospital, and the University of Washington have found a new potential target for drug development in the fight against flu.
Current flu vaccines must be created before flu strains predicted to be prevalent in the next flu season. As a result, they are not necessarily a direct match for the strain actually prevalent in any given flu season. In addition, the influenza virus mutates quickly, with different strains causing seasonal epidemics each year. Having a specific drug or a better way of treating an infection, once it sets in, would be an improvement.
“Once an infection starts, it’s too late for vaccines,” says Edward Dennis, professor of chemistry and biochemistry, and professor of pharmacology at UC San Diego, thus the urgent need for drugs to combat the influenza virus.
According to the Centers for Disease Control and Prevention, strains like H5N1 and H7N9—known as bird flu—kill about 60 percent of the people they infect.
The team found that omega-3 fatty acids, known as the lipids DHA and EPA, might be therapeutic targets for fighting the flu. Produced by all humans, they are known to be involved in resolving inflammation.
Led by Alan Aderem, co-founder of the Institute for Systems Biology, the researchers took a holistic, systems biology approach to study the interaction between the flu virus and patients. What made this particular flu study unique is that the team included an analysis of lipid molecules that regulate inflammation in their study. Typically, systems biology approaches are concerned with proteins, genes and other chemicals, while lipids are not often part of the picture.
The research team studied 141 different lipids and their breakdown products, and incorporated them into networks of genetic and proteomic host responses in mice to two different strains of the flu virus, one mild and one severe. They found that infection by the mild flu strain caused an inflammatory response followed by a distinct anti-inflammatory response. In contrast, infection by the severe H1N1 strain did not cause two distinct responses but caused a mixed inflammatory response, implying that H1N1 disturbed normal control of inflammation. The researchers found that many of the results from the mouse model were also observed in humans by studying nasal wash samples collected from flu-infected patients.
Understanding how the flu virus interacts with the human immune system, including the role of lipid mediators, could reveal important new drug targets. “If we can perturb the balance between pro- and anti-inflammatory responses in flu patients, we can help them regulate their immune systems to control their infections,” says Vincent Tam, a scientist involved in the study, published in the journal Cell.
Manufacturing and distributing vaccines takes a long time. “Because of this, drugs are critically important to combat flu infections,” says Aderem. “But at the moment, we have very few drugs at our disposal, and resistance is already beginning to appear against our limited arsenal.”
July 12, 2013