New Link Between Influenza Infection Pathway and Genetic Ancestry

A new study looked at the differences in how various cell types respond to viral infection and these findings can be useful to handle COVID-19.

Differences in immune pathway activation to influenza infection between individuals of European and African genetic ancestry were found in new research at the University of Chicago. The study was published in the journal Science.

“The lab has been interested in understanding how individuals from diverse populations respond differently to infectious diseases,” said first author Haley Randolph, a graduate student at UChicago.

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‘The immune response differences to influenza influenced by genetic ancestry and environmental effect correlate with COVID-19 disease severity.’

Researchers examined the gene expression patterns in specialized immune cells present in blood using single-cell RNA-sequencing. These cells play important roles in the body’s response to infection.

They collected these cells from men of European and African ancestry and then exposed the cells to flu in a laboratory setting.

This allowed them to examine the gene signatures of a variety of immune cell types and determine how infection with the flu virus affected each cell type’s gene expression.

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The results showed that individuals of European ancestry showed an increase in type I interferon pathway activity during early influenza infection.

“Interferons are proteins that are critical for fighting viral infections,” said senior author Luis Barreiro, Ph.D., Associate Professor of Medicine at UChicago.

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Similarly, In COVID-19, the type I interferon response has been associated with differences in the severity of the disease.

This increased pathway activation correlated with greater capacity to hinder the replication of the virus and a greater capacity to limit viral replication at a later time point.

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Inducing a strong type I interferon pathway response early upon infection stops the virus from replicating and may therefore have a direct impact on the body’s ability to control the virus.

A variety of differences in gene expression across different cell types indicate that the immune response variation cannot be isolated to a single type of immune cell, but rather connects a constellation of cells that work together to fight disease.

Such a difference 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 due to the flu than any other racial group.

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

Differences in susceptibility to viral infection may extend beyond the flu virus; When the researchers compared a list of genes associated with differences in the severity of COVID-19 disease, many of the same genes showed significant differences in their expression after flu infection between individuals of African and European ancestry.

The researchers are exploring this and other related questions in more detail. The hope is to figure out which factors contribute to the differences in the interferon response, and immune responses more broadly, to better predict individual disease risk.

Source-Medindia