Studies reveal a link between immune pathway responses to influenza and genetic ancestry

Transmission electron micrograph of influenza A virus, late passage. Credit: CDC

A new study at the University of Chicago found differences in the activation of immune pathways against influenza infection between individuals of genetic ancestry in Europe and Africa. Many of the genes associated with these differences in the immune response to influenza are also enriched among the genes that correlate with the severity of COVID-19 disease.This study was conducted on November 26th Chemistry.

“The lab was interested in understanding how individuals in diverse populations respond differently to infectious diseases,” said Haley, a graduate student at the University of Chicago. Randolph says. “In this study, we wanted to see the difference in how different cell types respond to viral infections.”

Using a single-cell RNA sequence, researchers could investigate Gene expression pattern Peripheral blood mononuclear cells cell, Professional diverse set Immune cells It plays an important role in the body’s response to infection.They collected these cells from European and African men ancestor The cells were then exposed to the flu in the laboratory. This allows the team to look at the genetic signatures of different immune cell types. Influenza virus It affected the gene expression of each cell type.

The results showed that individuals of European ancestry showed increased type I interferon pathway activity during the early stages. Influenza infection..

“Interferon is an essential protein in battle Virus infectionDr. Luis Barreiro, senior author and associate professor of medicine at the University of Chicago, said: “For example, in COVID-19, type I interferon response is associated with different disease severities.”

Moreover, this increased pathway activation correlated with a greater ability to prevent viral replication and, at a later point in time, a greater ability to limit viral replication. “Inducing a strong type I interferon pathway response early in the infection can stop the replication of the virus and can directly affect the body’s ability to control the virus,” says Barreiro. “Surprisingly, this central route to defense against the virus seems to be the most divergent between African and European individuals.”

Researchers have confirmed that there are various differences in gene expression between different cell types. Immune response Mutations cannot be separated into a single type of immune cell, but connect the constellations of cells that work together to fight the disease.

Such differences in immune pathway activation can contribute to the disparity in influenza outcomes between different racial groups.Non-Hispanic Black Americans Likely to be hospitalized for the flu More than any other racial group.

However, researchers quickly point out that these results are not evidence of genetic differences in disease susceptibility. Instead, other environmental and lifestyle factors that may differ between racial groups may affect gene expression, which may affect the immune response.

“There is a strong relationship between the interferon response and the proportion of the African genome, which may seem genetic, but it’s not that simple,” says Barreiro. “Genetic ancestors also correlate with environmental differences. Much of what we see can be the result of other disparities in our society, such as systematic racism and medical inequality. There is a specific genetic variation, indicating that genetics plays some such role. Genetic differences It is not enough to fully explain the difference in interferon response. “

These differences in susceptibility to viral infections can extend beyond the influenza virus.When researchers compare the list of gene In relation to the different severity of COVID-19 disease, many of the same genes showed significant differences in post-influenza expression between individuals of African and European descent.

“We did not study samples of COVID-19 patients as part of this study, but duplication between these gene sets is some fundamental biological difference affected by genetic ancestry and environmental influences. It suggests that there may be a result of COVID-19. “

Researchers are investigating this and other related questions in more detail. They expect a broader understanding of which factors contribute to the difference between interferon and immune responses in order to more accurately predict individual disease risk.

The title of this study is “Effects of genetic ancestors on response to viruses”. infection Additional authors include Mari Shiratori and João Barroso-Batista from the University of Chicago, Jessica K. Fiege, Beth K. Thielen, Clayton K. Mickelson, and Ryan A. Langlois from the University of Minnesota.

Severity of COVID-19 cases: How genetic differences put immune cells at a disadvantage

For more information:
Haley Randolph et al, genetic ancestral effects on response to viral infections are widespread, but cell-type specific. Chemistry (2021). DOI: 10.1126 / science.abg0928..

Quote: Immune pathway response to influenza and genetic ancestors obtained from on November 25, 2021 (2021) The relationship with (November 25) was found in the investigation.

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Studies reveal a link between immune pathway responses to influenza and genetic ancestry

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