Influenza causes heart complications by directly affecting the heart

Influenza causes heart complications by directly affecting the heart

Credit: Unsplash/CC0 Public Domain

Researchers have shown for the first time in mice that heart problems associated with influenza are not caused by severe inflammation of the lungs, as has long been expected.

Instead, the Ohio State University study revealed that the electrical malfunctions and heart scarring observed in some of the sicker influenza patients result from direct influenza infection of heart cells.

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

said lead author Jacob Yount, associate professor of microbial infection and immunity at Ohio State College of Medicine.

“It proves that it is direct infection of the heart that leads to these complications. Now we need to know what direct infection does: does it kill heart cells? Does it have long-term repercussions? Does repeated infection lead to heart complications that build up over time? There are a lot of questions Now we have to answer it.”

The study was published today in the journal science progress.

It has been proven for some time that hospitalized flu patients can develop heart problems. A 2020 study found that about 12% of adults in the United States who were hospitalized with influenza over an eight-year period developed sudden and serious cardiac complications.

Yount has studied influenza for years, and his lab developed a mouse model that lacks IFITM3, the gene that codes for a key protein in clearing the innate immune system of viral infections. In a 2019 study, his team found that mice with influenza that lacked the IFITM3 gene were more likely to develop heart problems.

These mice are not only highly susceptible to influenza, but are also deficient in the same antiviral protein that some people lack as well: about 20% of Chinese and 4% of Europeans have a genetic variant that causes a deficiency in IFITM3.

Yount, who is also co-director of the emerging viruses and pathogens program at the Ohio Institute of Infectious Diseases, said.

In this study, researchers modified the genome of the H1N1 influenza strain so that the virus could not hijack heart cells to make copies of itself. They injected the modified virus and a control virus into normal mice and mice lacking IFITM3.

Both viruses caused lung and systemic infections and generated high concentrations of viral particles in mice, but the variant virus was not detected in normal mouse heart cells and was present at significantly lower concentrations in hearts of IFITM3-deficient mice. These results allowed direct comparisons of mouse hearts with and without robust viral replication.

The researchers discovered less heart muscle damage, fewer biomarkers of cell injury, less scarring, or fibrosis in heart tissue, and reduced electrical signaling problems in the hearts of mice that received the genetically modified virus.

“We have this mouse model and this virus that allowed us to distinguish between acute pneumonia and direct replication of the virus in the heart. We haven’t been able to separate these two things in the past,” Yount said. “If you don’t have the virus reproducing aggressively in the heart, you won’t see the same electrical abnormalities or the same fibrotic response.”

There is still much to learn. Influenza tends to focus most of its efforts on infiltrating the lungs, but is generally not present in the blood or other organs. But it gets to the heart — and figuring out how that happens is part of the ongoing work at Yount’s lab.

It’s too soon to know how this research might affect the treatment of hospitalized flu patients with heart complications, but Yount said these findings suggest clearing up the viral infection could be key to reducing the problematic effects of flu on the heart.

“One of the things this tells us is that this is another reason to get the flu shot, because you don’t want your heart to get the flu — that’s a possibility,” he said.

This work was supported by grants from the National Institutes of Health, the Ohio State University Presidency Fellowship, the Ohio State Institute of Infectious Diseases, the Ohio State College of Medicine and the National Science Foundation.

Co-authors are Adam Kenny, Naresh Kumar, Bing Chen, Adrian Eddy, Lizzie Zhang, Ashley Zane, Nahara Vargas-Maldonado, Samuel Speak, Jeffrey Kawahara, Parker Deans, Lisa Dorn, Federica Ocornero, Jianji Ma, Hua Chu, Morogisan Rajaram and Chuanxi Kay, all from Ohio, and Stephanie Aaron and Clara Gilbert and Ryan Langlois from the University of Minnesota.

Gene mutation linked to heart complications associated with influenza

more information:
Adam Kenny et al, Replication of influenza virus in cardiomyocytes causes cardiac dysfunction and fibrosis, science progress (2022). DOI: 10.1126 / sciadv.abm5371.

Provided by Ohio State University

the quote: Influenza causes heart complications by directly infecting the heart (2022, May 11) Retrieved May 13, 2022 from

This document is subject to copyright. Notwithstanding any fair dealing for the purpose of private study or research, no part may be reproduced without written permission. The content is provided for informational purposes only.

2022-05-11 18:00:06

Leave a Comment

Your email address will not be published. Required fields are marked *