“We’ve shown that even if you have a very severe infection in your lungs, if you’re taking a virus that can’t replicate in your heart, you won’t be able to replicate it,” said lead author Jacob Yount. suffer from cardiovascular complications. at Ohio State College of Medicine.
“It demonstrates that it is direct infection of the heart that is leading to these complications. Now we need to find out what the direct infection does: Does it kill heart cells? There are a lot of questions we need to answer.”
At one time it was thought that hospitalized febrile patients might have heart problems. In a 2020 study, 12% of adults hospitalized with the flu in the United States over 8 years developed sudden and severe heart problems.
Yount has been studying influenza for many years, and his lab has developed a mouse model that does not contain IFITM3, a gene that represents a protein important in clearing viral infections in the endocrine system. A 2019 study by his team found that mice infected with the IFIDM3 mutant gene had a higher risk of heart problems.
These mice are not only susceptible to inflammatory flu, but also have a deficiency in the same antiviral protein that some people do not: about 20% of the Chinese population and 4% of Europeans have a variant. genetic basis for IFITM3 deficiency.
Yount, program co-director of the Viruses and Emerging Pathogens Program, said: “We know these people are more susceptible to severe flu, and our mouse study shows that they are also susceptible to the virus. heart disease than with the flu.” Ohio State Institute of Infectious Diseases.
Research on genomic alteration
For this study, the researchers mutated the gene of the H1N1 flu strain so that the virus could not get into heart cells to replicate itself. They injected mutant and control viruses into normal and IFITM3-free mice.
Both viruses cause pneumonia (pneumonia) and systemic inflammation and produce high concentrations of virus particles in mice, but the mutant virus was not detected in the heart cells of normal mice and is present. present at significantly lower concentrations in the hearts of mice lacking IFITM3. These findings allow a direct comparison between the hearts of mice with and without strong viral replication.
The researchers found less heart muscle damage, fewer biomarkers for cell damage, less scarring of heart tissue or fibrosis, and problems with electrical signaling in the hearts of mice infected with the mutant virus. gene change.
“We have this mouse model, and this virus allows us to distinguish between severe pneumonia and direct replication of the virus in the heart,” Yount said. “If you don’t have the virus multiplying aggressively in your heart, you won’t see the same electrical abnormalities or fibrotic responses.”
There is still a lot to learn. Influenza focuses most of its efforts on entering the lungs, but often the bloodstream or other organs. But it gets to the heart – and figuring out how this happens is part of ongoing work in Yount’s lab.
It’s too early to say how this study will impact the treatment of hospitalized flu patients with heart problems, but these findings suggest that eradicating viral infection is important. in reducing febrile cardiac complications.
“The one thing this tells us is that this is another reason to get a flu shot, because you don’t want your heart to get infected – and that’s a possibility,” he said.