“We have shown that even if you have a very severe lung infection, if you use this virus that cannot multiply in the heart, you are not getting these heart complications,” said lead author Jacob Yunt, an associate professor. at Ohio Medical College.
“It proves that a direct heart infection causes these complications. Now we need to find out what a direct infection does: does it kill heart cells? Does it have long-term branching? Do re-infections have heart complications that increase over time?” a lot of questions that need to be answered. ”
It has been found for some time that patients with fever who are in the hospital may have heart problems. In a 2020 study, 12% of adults hospitalized with the flu in the United States for eight years developed sudden serious heart problems.
Yant has been studying inflammatory influenza for many years, and his lab has developed a mouse model that does not contain IFITM3, a gene that is an important protein in eliminating viral infections of the endocrine system. A 2019 study by his team found that mice infected with the mutated IFIDM3 gene are at greater risk of developing heart problems.
These mice are not only prone to 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 that these people are more susceptible to severe flu infections, and our studies in mice show that they are also more susceptible to heart complications from the flu,” said Yant, also co-director of the Virus and New Pathogens Program. Ohio Institute of Infectious Diseases.
Genome change study
For this study, scientists mutated the gene for the H1N1 flu strain so that the virus could not pass into heart cells to copy itself. They administered the mutated virus and control virus to conventional mice and mice without IFITM3.
Both viruses caused pneumonia (pneumonia) and systemic inflammation and caused high concentrations of viral particles in mice, but the mutated virus was not detected in normal mouse heart cells and was present in much lower concentrations in IFITM3 deficient mice. These findings allowed a direct comparison of the hearts of mice with strong viral replication and without it.
The researchers found less damage to the heart muscle, fewer biomarkers for cell damage, fewer heart tissue scars or fibrosis, and problems with the electrical signal in the hearts of mice infected with the genetically modified virus.
“We have this mouse model and this virus that has allowed us to distinguish between severe pneumonia and direct replication of the virus in the heart. Previously, we could not separate these two things,” Yunt said. “If you don’t have a strong replication of the virus in your heart, you don’t see the same electrical disturbances or the same fibrotic response.”
There is still a lot to learn. Most of the effort with the flu is focused on penetrating the lungs, but usually the blood or other organs. But it goes to the heart – and figuring out how it happens is part of the ongoing work at Yunt’s lab.
It is too early to say how this study will affect the treatment of flu patients who are hospitalized with heart problems, but these findings suggest that eliminating the viral infection is important to minimize complications of febrile heart complications.
“It tells us one thing, that’s another reason to get vaccinated against the flu, because you don’t want your heart to get the flu – and that’s an opportunity,” he said.