When otherwise healthy people get the flu, they can usually get over it after a few days of feeling lousy. But sometimes people develop life-threatening complications that affect their heart when they get an influenza virus infection. Now researchers have found a genetic susceptibility that seems to increase the likelihood of heart trouble in flu patients, helping to explain these complications and potentially prevent them one day. The findings have been reported in the Proceedings of the National Academy of Science (PNAS).
A gene called IFITM3 encodes for a protein that is critical to the intial stages of the immune response in people. When it carries mutations, people are more likely to be hospitalized or die due to the flu. In mice engineered to lack the IFITM3 gene, flu infections triggered heart trouble more often than in normal mice.
"By knocking out this gene in mice, and infecting them with various strains of flu, we were able to show that this gene's absence increases the chances of heart abnormalities - decreased heart rate and irregular heartbeat and death," said study leader Jacob Yount, an assistant professor of microbial infection and immunity at The Ohio State University (OSU). "There's been no known link between this gene and flu-related heart complications until now."
The research team also found that in the mice, heart tissue was infected with the virus, and that fibrosis was occurring - collagen was building up. "Too much of this collagen can cause 'bumps in the road' that could disrupt the electrical flow of the heart - that could explain the erratic heart rhythms we saw in this experiment," Yount explained.
Every flu season presents us with a different virus; they have varying severities and the vaccines we use to prevent them have variable levels of efficacy. Every year around eight percent of Americans come down with the flu. A mild season might cause 12,000 deaths, while more severe outbreaks might kill as many as 79,000 people, according to the Centers for Disease Control and Prevention.
Now that we know more about how serious complications can arise during flu infections, we may soon prevent them from happening, or deal with them in more effective ways once they do.
The researchers also found that the incidence of heart trouble was dependent on how virulent the flu strain was. The weakest strains didn’t cause heart trouble in their mouse model while the worst ones led to lasting heart damage and were most likely to cause death.
"Flu can exacerbate underlying heart disease, but it can also affect the hearts of people who are otherwise healthy, typically in cases where people are so sick with the flu that they've been hospitalized," said Yount.
"A lot of people have assumed that systemic inflammation from the infection stresses or harms the heart, but this new finding suggests that some people may be genetically predisposed to these complications," Yount added.
Mutations in IFITM3 are fairly common, with previous research indicating that about twenty percent of Chinese people and about four percent of people of European descent carrying mutations in the gene.
Yount’s lab is now working on experimental therapies using the mouse model. "It's exciting to now have a model to help us answer more questions about why flu is causing these heart problems and to test drugs that might help people," he said. "For now, there's no treatment that specifically focuses on the cardiac complications from the flu."
Sources: AAAS/Eurekalert! via OSU, PNAS
