The latest research conducted at the University of Chicago has found differences in immune pathway activation to influenza infection between individuals of European and African genetic ancestry. Many genes associated with the immune response to influenza are also present in genes that are associated with COVID-19 severity. The study was published on the 26th of November in Science.
Haley Randolph, a UChicago graduate student, said that the lab was interested in learning the ways that different groups of people react to infectious diseases. “In this study we wanted to examine the differences in the way different types of cells respond to viral infections.”
Through single-cell RNA-sequencing the researchers were able to study the expression patterns of genes in peripheral mononuclear blood cells. a variety of immune cells specialized to play a crucial role in the body’s response to infection. These cells were derived from African and European ancestral lineages and then exposed to the flu in a laboratory. This allowed the researchers to study the genes of various immune cell types and determine how the flu virus affected the cell’s gene expression.
The results showed that people of European descent had an increase in the type 1 interferon pathway activation during the flu season’s early stages.
Luis Barreiro (Associate Professor of Medicine at UChicago) stated that interferons are proteins vital to fight viral infections. “In COVID-19, for instance, the type I interferon response has been linked with different degrees of severity of the disease.”
Additionally, this higher pathway activation was linked to more capacity to stop the replication of the virus, and an increased capacity to stop the spread of the virus at a later date. “Inducing a strong interferon pathway of type I immediately following infection prevents the virus from replicating and therefore has an impact directly on the body’s ability to manage the virus,” said Barreiro. “Unexpectedly this key pathway to protect us against viruses appears to be the most distinct among people of African and European ancestry.”
Researchers observed a variety in gene expression among different cell types. This indicates that the immune response variation is not restricted to a specific kind of immune cell but rather connects many cells that collaborate to fight diseases.
A variation in immune pathway activation could contribute to disparities in influenza outcomes between different racial groups; Non-Hispanic Black Americans are more likely to be hospitalized because of the flu than any other racial group.
Researchers are quick to point this out: These results don’t support genetic differences in susceptibility to disease. Instead, other environmental and lifestyle factors that are different between racial groups may be influencing gene expression which may in turn affect the immune response.
Barreiro stated that there is a significant correlation between interferon response and African ancestry. This could lead you to believe it’s genetic. “Genetic ancestry also correlates with environmental variations. A lot of what we’re capturing could be due to other social disparities that are rooted in racism, like systemic racism and healthcare inequities. While some of the differences that we observe in the paper could be due to specific genetic differences, showing that genetics do play a part, genetic differences aren’t enough to explain the differences in the interferon response.”
The differences in vulnerability to viral infection may not be limited to flu viruses. Researchers compared a set of genes associated with different severity levels of COVID-19. Many of these genes showed significant differences following influenza in people of African and European descent.
“We did not examine COVID-19 patient samples as part of this study, however the overlap between these gene sets suggests there could be some fundamental biological differences caused by genetic ancestry and environmental factors, that could be the reason for the differences we see in COVID-19 results,” Barreiro said. Barreiro.
The researchers are exploring these and other related questions in more details. The aim, they say, is to discover which factors contribute to the differences in the interferon response, and immune responses in general, to better predict individual disease risk.
University of Chicago Medical Center
Randolph, H.E., et al. (2021) Genetic ancestry effects on the response to viral infections are widespread, however, they are cell type specific. Science. doi.org/10.1126/science.abg0928.
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