May 18, 2022
Influenza virus directly infects the heart and causes cardiac complications
Researchers believed that the heart problems were caused by raging infections of the lungs alone

Researchers for the first time have demonstrated that the flu virus directly infects the heart, and that cardiac problems during infections are not caused by inflammation of the lungs alone. While the team had spotted viral particles in the heart tissue in previous investigations, they could not say for sure if the presence of the virus was causing direct heart damage. In the new study, the researchers were able to show that scarring of heart tissue and electrical malfunctions were a direct consequence of the infection by the flu virus. Mice were infected with a genetically modified flu virus that did not have the capacity to infect heart tissue. The mice did not show any cardiac complications but developed classic symptoms of flu.

Lead author of the paper Jacob Yount says, “We showed that even when you have a very severe infection in the lungs, if you’re using that virus that can’t replicate in the heart, you don’t get those cardiac complications. It proves it’s direct infection of the heart that’s driving these complications. Now we need to figure out what direct infection does: Is it killing heart cells? Does it have long-term ramifications? Do repeated infections have heart complications that build up over time? There are a lot of questions now for us to answer.”

Yount has been studying flu for years in his lab, and has developed a mouse model lacking the IFITM3 gene, that codes for a protein crucial for the innate immune system to clear viral infections. In previous research, his team found that mice lacking the IFITM3 gene were at a higher risk of developing cardiac infections. Some people lack the same antiviral protein, about 20 per cent of Chinese and 4 per cent of Europeans have a genetic variant that causes a deficiency of IFITM3. Yount says, “We know those people are more susceptible to severe flu infections, and our mouse research would suggest they’re also more susceptible to heart complications with the flu.”

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The altered H1N1 strain that could not infect heart cells was introduced to mice with and without IFITM3. The modified virus was undetected in the normal mice, and was detected in much lower concentrations in the heart cells of mice deficient in IFITM3. Yount says, “We have this mouse model and this virus that allowed us to distinguish between the severe lung inflammation and the direct replication of the virus in the heart. We hadn’t been able to separate those two things in the past. If you don’t have the virus replicating strongly in the heart, you don’t see the same electrical abnormalities or the same fibrotic response.”

The virus focuses on infecting lung cells, and does not travel through the blood stream to infect other organs. The researchers want to find out how it gets to the heart. It is too soon to say if the research result in any changes in the treatment of flu patients. Yount says, “One thing this tells us is that this is another reason to get your flu shot, because you don’t want your heart to get infected by the flu – and it is a possibility”.

A paper describing the findings has been published in Science Advances.

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