They explain how genetics can protect us against the flu and Covid-19

Madrid

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An investigation carried out in the
University of Chicago
(USA) has found differences in the immune response to influenza between individuals of European and African genetic descent. Many of the genes that were associated with these differences in the immune response to influenza are also found among genes that correlate with the severity of Covid-19.

The study, published in
«Science»
, could help explain population-level differences in the immune response to the flu virus and perhaps Covid-19 as well.

The laboratory of
Luis Barreiro
He has been researching for years how people from diverse populations respond differently to infectious diseases. Now, the first author points out Haley Randolph, “In this study we wanted to look at the differences in how various cell types respond to viral infection.”

Researchers, through single cell RNA sequencing, were able to examine gene expression patterns in peripheral mononuclear blood cells, a disparate set of specialized immune cells that play important roles in the body’s response to infection.

In study we wanted to observe the differences in how various types of cells respond to viral infection

They collected these cells from people of European and African descent and then exposed them to the flu virus in a laboratory. This made it possible to examine the gene signatures of a variety of immune cell types and determine how infection with the influenza virus affected the gene expression of each cell type.

The results showed that individuals of European descent exhibited increased activity of the type I interferon pathway during early influenza infection.

“The interferones they are proteins that are essential to fight viral infections, ”explains lead author Luis Barreiro. “In Covid-19, for example, the response to type I interferon has been associated with differences in the severity of the disease.”

Furthermore, this greater activation of the pathway was related to a increased ability to hamper virus replication and to limit viral replication subsequently.

‘Induction of a strong response of the type I interferon pathway early in infection stops virus replication and therefore may have a direct impact on the body’s ability to control the virus», Emphasizes Barreiro.

Surprisingly, they write, this central avenue of our defense against virus appears to be one of the most divergent between individuals of African and European descent.

The researchers appreciated a variety of differences in gene expression in different cell types, indicating that the variation of the immune response cannot be isolated in a single type of immune cell, but rather connects a constellation of cells working together to fight disease.

Such a difference in immune pathway activation could contribute to disparities in flu outcomes between different racial groups. Thus, non-Hispanic African Americans are known to have more likely to be hospitalized due to the flu than any other racial group.

However, researchers are quick to point out that these results are not evidence of genetic differences in disease susceptibility. And they point out that orother environmental and lifestyle factors that may differ between groups Racial races could influence gene expression, which in turn can affect the immune response.

There is a strong relationship between the response to interferon and the proportion of the genome that is of African descent, which might make you think it is genetic, but it is not that simple

«There is a strong relationship between the response to interferon and the proportion of the genome that he is of African descent, which might make you think he is genetic, but it is not that simple, “says Barreiro. «Genetic ancestry is also correlated with environmental differences».

He adds: “Much of what we are appreciating could be the result of other disparities in our society, such as systemic racism and inequities in health care. Although some of the differences that we show in the article may be related to variations specific genetics, which shows that the genetics does play a role, these genetic differences are not sufficient to fully explain the discrepancies in the response to interferon. ‘

Now, they write, “because of the central role that interferons play in conferring antiviral activity on host cells, our findings have potential clinical implications not only for influenza infection but also for other viruses, including SARS-CoV. -2, for which the timing and magnitude of the interferon-mediated action antiviral responses are associated with disease progression and severity».

There may be some underlying biological differences, influenced by genetic ancestry and environmental effects

Furthermore, they argue that these differences in susceptibility to viral infection may extend beyond the influenza virus; when the researchers compared a list of genes associated with differences in Covid-19 severity, many of the same genes showed significant differences in their expression after influenza infection between individuals of African and European descent.

‘We did not study samples from Covid-19 patients as part of this study, but the overlap between these gene sets suggests that there may be some underlying biological differences, influenced by genetic ancestry and environmental effects, which could explain the disparities that we see in Covid-19 “, concludes Barreiro.

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