Instead, the Ohio State University study revealed, the electrical malfunctions and heart scarring seen in some of the sickest flu patients are caused by direct influenza infection of cardiac cells.

The research team had seen flu viral particles in cardiac cells of infected mice in previous work, but couldn’t say for sure their presence in the heart was driving cardiac damage. When researchers infected mice with a genetically altered flu virus that wasn’t able to replicate in heart cells, the mice developed classic inflammatory flu symptoms — but no cardiac complications.

“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,” said lead author Jacob Yount, associate professor of microbial infection and immunity in Ohio State’s College of Medicine.

“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.”

The study is published today (May 11, 2022) in the journal Science Advances.

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

Yount has studied flu for years, and his lab developed a mouse model lacking IFITM3, the gene that codes for a key protein in the innate immune system’s clearance of viral infections. His team found in a 2019 study that flu-infected mice lacking the IFITM3 gene were at higher risk for developing cardiac issues.

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

“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,” said Yount, also a program co-director of the Viruses and Emerging Pathogens Program in Ohio State’s Infectious Diseases Institute.

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

Both viruses caused lung and systemic inflammation and generated high concentrations of viral particles in the mice, but the altered virus was undetected in normal mouse heart cells and present in significantly lower concentrations in the IFITM3-deficient mouse hearts. These findings allowed for direct comparisons between the hearts of mice with and without robust virus replication.

The researchers detected less heart muscle damage, lower biomarkers for cell injury, less scarring, or fibrosis, of heart tissue and decreased electrical signaling problems in the hearts of mice that received the genetically altered virus.

“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,” Yount said. “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.”

There is still a lot to learn. Influenza tends to focus most of its efforts on infiltrating the lungs, but generally isn’t present in the blood or other organs. But it does get to the heart — and finding out how this happens is part of continuing work in Yount’s lab.

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

“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,” he said.

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

Co-authors include Adam Kenney, Naresh Kumar, Peng Chen, Adrian Eddy, Lizhi Zhang, Ashley Zani, Nahara Vargas-Maldonado, Samuel Speaks, Jeffrey Kawahara, Parker Denz, Lisa Dorn, Federica Accornero, Jianjie Ma, Hua Zhu, Murugesan Rajaram and Chuanxi Cai, all from Ohio State, and Stephanie Aron, Clara Gilbert and Ryan Langlois of the University of Minnesota.

Now, a new study in the journal PLOS ONE provides interdisciplinary support for connections between livestock dairying and the rise of social complexity in the eastern steppe. Using proteomic analysis of human dental calculus from sites in the Mongolian Altai, the researchers demonstrate a shift in dairy consumption over the course of the Bronze Age.

By tracking the consumption of dairy among populations in the Altai Mountains in Mongolia, researchers revealed the critical role of domesticated sheep, goats and cattle in ancient economies. The adoption of ruminant livestock eventually led to population growth, the establishment of community cemeteries and the construction of large monuments. While these pronounced changes occurred in tandem with the earliest evidence of horse dairying in Mongolia, the consumption of horse dairy remained a relatively novel practice until later periods.

Thus, the spread of herds into the Mongolian Altai resulted in immediate changes to human diets, with a delay in subsequent social and demographic transformations, said study lead author Alicia Ventresca Miller, assistant professor of anthropology at the University of Michigan.

“As we push back the dates of the introduction of livestock, we need to rethink the pace of social change, which may occur on much longer timescales,” she said.

Ventresca Miller and colleagues from U-M and the Max Planck Institute for the Science of Human History in Germany extracted proteins from calculus samples to identify caseins and whey associated with ruminant and horse dairy. Results were interpreted in consultation with researchers from the National University of Mongolia and National Museum of Mongolia, in an effort to clarify how ancient societies changed after the adoption of domesticated livestock.

Dramatic social changes and monumental constructions were fueled by a long-term dependence on sheep, goats and cattle, Ventresca Miller says. This is supported by finds of mostly ruminant bones in large monumental Khirgisuurs in the Altai Mountains, while in other areas of Mongolia horse bone deposits have been identified along with ruminants.

“These new results might allow for a shift in our understanding of Bronze Age dynamics,” said Tsagaan Turbat, professor of archaeology and anthropology at the National University of Mongolia.

Turbat believes that Deer Stone-Khirgisuur complexes, the most studied in the region, may have originated from Sagsai groups in the Altai Mountains.

The current study pushes back the earliest date of horse dairying in the eastern steppe associated with Sagsai burials to about 1350 B.C. As initial evidence of horse milk consumption is rare, this may have been a novelty since horses were an important feature of ritual life, the researchers say.

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“Little is known about the mechanism behind drivers of yields and protein content in wheat production,” said the University of Adelaide’s Dr Scott Boden, School of Agriculture, Food and Wine who led the research.

“Discovering a gene that controls these two factors has the potential to help generate new wheat varieties that produce higher quality grain.

“As wheat accounts for nearly 20 per cent of protein consumed worldwide, the impact of this research can significantly benefit society by providing grains with a higher protein content, which could therefore help produce more nutritious food, such as bread and breakfast cereals.”

The work is the first known example where a forward-genetics screen of a mutant population has been used to identify a gene that controls reproductive development in wheat and insights from this research has the potential to help improve the nutritional and economic value of wheat.

“The genetic variation we identified provides a 15-25 per cent increase in protein content for plants grown in the field. These varieties also produce extra spikelets, known as paired spikelets,” said Dr Boden.

“We have not yet detected an increase in yield with the extra spikelets, but we hope a yield increase might come in elite varieties grown by farmers.

“The increase in protein content occurs without the trade-off of a reduced yield so this discovery has even better potential to provide economic benefit to breeders and growers than just the increased nutritional value by itself.

“Aside from the important outcome of this work for the future of wheat breeding, the research itself is of immense value to the scientific community as it provides an elegant example of new capabilities that are available to wheat research.”

The team expects that the new wheat varieties will be available to breeders in 2-3 years’ time, which could then translate to benefits for farmers in 7-10 years’ time.

The team’s findings were published in the journal Science Advances.

This project was funded by the Royal Society (UK), the Biological and Biotechnology Sciences Research Council (UK), the Australian Research Council (ARC), the South Australian Grain Industry Trust (SAGIT) and the University of Adelaide’s Waite Research Institute.

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Materials provided by University of Adelaide. Original written by Crispin Savage. Note: Content may be edited for style and length.