Mystery Unfolded Between Heart Problems and Inflammatory Flu: Soon to Humans
The research team looked at the viral particles in the cardiac cells of mice that had been affected in previous work, but could not confirm whether their presence in the heart was affecting it or not. When researchers infected mice with a genetically modified inflammatory flu virus that could not be replicated in cardiac cells, the mice developed classic inflammatory flu symptoms but no heart problems.
“We showed that even when you have a very severe infection in the lungs, if you’re using that virus that can’t replicate in the heart, you don’t get those cardiac complications,” said lead author Jacob Yount, associate professor in Ohio State’s College of Medicine.
“It proves it’s direct infection of the heart that’s driving these complications. Now we need to figure out what direct infection does: Is it killing heart cells? Does it have long-term ramifications? Do repeated infections have heart complications that build up over time? There are a lot of questions now for us to answer.”
It has been established for some time that hospital-admitted fever patients may develop heart problems. In a 2020 study, 12% of adults hospitalized with the flu in the United States for eight years had developed sudden, severe heart problems.
Yount has been studying the inflammatory flu for many years, and his lab has developed a mouse model that does not contain IFITM3, a gene that represents an important protein in eliminating viral infections of the endocrine system. A 2019 study by his team found that mice infected with the IFIDM3 mutated gene were at higher risk for developing heart problems.
These mice not only are susceptible to the inflammatory flu, but also have a deficiency of the same antiviral protein that some people do not have: about 20% of the Chinese population and 4% of Europeans have a genetic variant that causes IFITM3 deficiency.
“We know those people are more susceptible to severe flu infections, and our mouse research would suggest they’re also more susceptible to heart complications with the flu,” said Yount, also a program co-director of the Viruses and Emerging Pathogens Program in Ohio State’s Infectious Diseases Institute.
Genome Altering Study
For this study, the researchers had mutated the gene of the H1N1 flu strain so that the virus could not pass on to the heart cells to copy itself. They injected the mutated virus and the control virus into normal mice and mice without IFITM3.
Both viruses caused lung (pneumonia) and systemic inflammation and produced high concentrations of virus particles in mice, but the mutated virus was not detected in normal mouse heart cells and was present at significantly lower concentrations in IFITM3-deficient mouse hearts. These findings allowed direct comparisons between the hearts of mice with and without strong viral replication.
The researchers found less heart muscle damage, fewer biomarks for cell injury, less scarring of heart tissue or fibrosis, and electrical signal problems in the hearts of mice infected with the genetically modified virus.
“We have this mouse model and this virus that allowed us to distinguish between the severe lung inflammation and the direct replication of the virus in the heart. We hadn’t been able to separate those two things in the past,” Yount said. “If you don’t have the virus replicating strongly in the heart, you don’t see the same electrical abnormalities or the same fibrotic response.”
There is still a lot more to learn. Influenza focuses most of its efforts on infiltrating the lungs, but usually into the bloodstream or other organs. But it goes to the heart – and finding out how this happens is part of the ongoing work in Yount’s lab.
It is too early to tell how this research will have an impact on the treatment of hospital-admitted flu patients with heart problems, but these findings suggest that eliminating the virus infection is important in minimizing the complications of fever complications in the heart.
“One thing this tells us is that this is another reason to get your flu shot, because you don’t want your heart to get infected by the flu – and it is a possibility,” he said.