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How our genetic ancestry shapes our immune response to influenza

A new study has revealed how ancestry and associated genetic variation can explain population-level differences in the immune response to the influenza virus.

Susceptibility to infectious disease

One of the strongest sources of selection pressure in human evolution are pathogenic viruses. Before the modern era of travel, global pandemics were likely rare and confined to regional populations. These events, if geographically contained, may have driven local divergence in the frequencies of polymorphisms that control the immune response.  

Genetic variants that impact the immune response are well known. For example, researchers have identified over 120 genetic variants that predict the gene regulatory response to influenza A virus (IAV) in dendritic cells. Variation in the transcriptional response to IAV has also been observed to be correlated with genetic ancestry in monocytes. This highlights that genetic divergence between human populations plays a role in shaping the immune response. Nonetheless, these studies have been limited as they have only focussed on isolated cell types. It is also unclear as to whether these genetic ancestry effects are specific to distinct immune cell types.

Response to influenza infection

To overcome these limitations, researchers used single-cell RNA sequencing to quantify variation in response to influenza infection in peripheral blood mononuclear cells from European- and African-ancestry males. Their findings were published in Science.  

The team found that genetic ancestry effects were common but highly cell type specific. One exception to this was the overall pattern of genetic ancestry’s effects on the interferon (IFN) response following infection. Across all cell types, higher levels of European ancestry were associated with increased activity in type I IFN pathways during early infection. This in turn predicted reduced vial levels at later time points.

“Given the central role played by IFNs in conferring antiviral activity to 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 IFN-mediated antiviral responses are associated with disease progression and severity,” say the authors.

This study also reported that genetic ancestry-associated genes were enriched among genes correlated with COVID-19 severity. These findings could contribute to the observed differences observed between African and European COVID-19 susceptibility.

Image credit: canva