For the first time, researchers have shown that heart problems associated with the flu are not caused by inflammation in the lungs.
The electrical malfunction and heart scarring seen in some of the sickest flu patients are caused by the flu, according to the Ohio State University study.
The research team could not say for certain if the presence of flu viral particles in the heart was causing cardiac damage. The inflammatory flu symptoms that the mice developed when they were injected with a genetically altered flu virus were not related to heart problems.
Lead author Jacob Yount said that they showed that if you use a virus that can't replicate in the heart, you don't get those cardiac problems.
It proves that the heart is the cause of these problems. We need to figure out if direct infections kill heart cells. Does it have long-term consequences? Do repeated infections cause heart problems over time? There are a lot of questions for us to answer.
The study was published in the journal Science Advances.
It has been established that hospitalized flu patients can have heart problems. A study in 2020 found that 12% of adults who were hospitalized with the flu developed sudden, serious heart problems.
The lab of Yount has studied flu for years, and has developed a mouse model that lacks the IFITM3 gene, which is needed for the clearance of viral infections. His team found in a study that flu-infecting mice were more likely to develop cardiac issues.
Some people have a genetic variant that causes a deficiency of the IFIP3 which is why these mice are highly susceptible to the flu.
We know those people are more susceptible to severe flu infections, and our mouse research would suggest they are also more susceptible to heart problems with the flu, said Yount, also a program co-director of the Viruses and Emerging Pathogens Program.
The researchers altered the H1N1 flu strain's genome so that it wouldn't hijack heart cells to make copies of itself. They injected the altered virus and a control virus into the mice.
The altered virus was undetected in normal mouse heart cells and present in lower concentrations in the IFITM3 deficient mouse hearts, even though it caused lung and systemic inflammation and generated high concentrations of viral particles in the mice. The findings allowed for comparisons between the hearts of mice.
The researchers detected less heart muscle damage, lower markers for cell injury, less scarring, and decreased electrical signaling problems in the hearts of mice that received the genetically altered virus.
We have a mouse model that allows us to distinguish between lung inflammation and the direct replication of the virus in the heart. Yount said that they hadn't been able to separate the two things in the past.
There is still a lot to learn. Influenza tends to focus on infiltrating the lungs and not the blood or other organs. It gets to the heart and is part of the continuing work in Yount's lab.
It is too early to tell how this research will affect the treatment of hospitalized flu patients with cardiac problems, but Yount said these findings suggest clearing the viral infection could be key to reducing flu's problematic effects on the heart.
He said that this is another reason to get a flu shot, because you don't want your heart to get sick from the flu.
The work was supported by grants from the National Institutes of Health, Ohio State University, the Ohio State College of Medicine, and the National Science Foundation.
The co-authors are Adam Kenney, Naresh Kumar, Adrian Eddy, Lizhi Zhang, Nahara Vargas-Maldonado, Samuel Speaks, Jeffrey Kawahara, and Federica Accornero.
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The materials were provided by Ohio State University. Emily Caldwell wrote the original. Content can be edited for style and length.
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