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In a study on mice, the heart does not only affect pneumonia – ScienceDaily

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Researchers have shown for the first time in mice that heart problems related to the flu are not caused by rampant pneumonia, as has long been predicted.

Instead, a study by Ohio State University found that electrical failures and scarring of the heart that are observed in some of the most flu patients are caused by direct influenza infection of heart cells.

The research team had seen influenza virus particles in the heart cells of infected mice in previous work, but could not say for sure that their presence in the heart causes heart damage. When researchers infected mice with a genetically modified influenza virus that was unable to multiply in heart cells, mice developed classic symptoms of inflammatory flu – but without heart complications.

“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. microbial infection and immunity 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. ”

The study was published today (May 11, 2022) in the Journal Advances in science.

It has been established for some time that hospitalized flu patients may have heart problems. A 2020 study found that about 12% of adults in the U.S. hospitalized with the flu for eight years developed sudden serious heart complications.

Yant has studied the flu for years, and his lab has developed a mouse model that lacks IFITM3, a gene that encodes a key protein in the elimination of viral infections by the innate immune system. His team found in a 2019 study that influenza-infected mice without the IFITM3 gene are at greater risk for heart problems.

These mice are not only very susceptible to the flu, but also deficient in the same antiviral protein that some people lack: about 20% of Chinese 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.

For this study, scientists altered the genome of the H1N1 flu strain so that the virus could not capture heart cells to make copies of itself. They administered the altered virus and control virus to conventional mice and mice without IFITM3.

Both viruses caused pneumonia and systemic and caused high concentrations of viral particles in mice, but the altered virus was not detected in normal mouse heart cells and was present in much lower concentrations in the hearts of IFITM3-deficient mice. These findings allowed a direct comparison of the hearts of mice with and without reliable replication of the virus.

The researchers found less damage to the heart muscle, smaller biomarkers of cell damage, fewer scars or fibrosis of heart tissue and a reduction in electrical signaling problems in the hearts of mice that received 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. Influenza usually focuses most of its efforts on penetrating the lungs, but is not usually present in the blood or other organs. But it gets to the heart of the heart – and figuring out how it happens is part of a long work in Yunt’s lab.

It is too early to say how this study could affect the treatment of hospitalized flu patients with heart complications, but Junt said these findings suggest that clearing the viral infection may be key to reducing the problematic effects of the flu on the heart.

“One thing it tells us is 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.

This work was supported by grants from the National Institutes of Health, a presidential scholarship from Ohio State University, the Ohio Institute of Infectious Diseases, Ohio Medical College, and the National Science Foundation.

Co-authors include Adam Kenny, Naresh Kumar, Peng Chen, Adrian Eddie, Lizhi Zhang, Ashley Zani, Nahara Vargas-Maldonada, Samuel Spike, Jeffrey Cavahara, Parker Denz, Lisa Dorn, Federico Aczean, Juju and Jiang, Jiang. , all from Ohio, as well as Stephanie Aron, Clara Gilbert and Ryan Langlois of the University of Minnesota.

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