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Genetic ancestry can explain population-level differences in immune response to the flu virus

23Strands News
23Strands News November 26, 2021

A new study aimed at explaining different responses to viral epidemics reveals that ancestry and associated genetic variation can explain population-level differences in the immune response to the flu virus and perhaps also to COVID-19.

Viruses are among the strongest sources of selection pressure in human evolution. However, before the modern era, widespread pandemics were likely rare. Instead, virus outbreaks were confined to regional populations. As most past viral epidemics were geographically contained, they may have driven differences in population responses to viral infections. While ancestry has been associated with differences in the responses to viruses, the genetic understanding of these variations remains unclear.

To better understand different population responses to influenza Haley Randolph and her team used a method called single-cell RNA sequencing of peripheral blood mononuclear cells (a type of blood sample used in research and toxicology) infected with influenza A. Samples from individuals with European and African genetic ancestry were tested in vitro (within the "glass", aka petri dish).

According to Randolph et al., infection led to gene signatures that diverged in a cell-type-specific manner, correlated with ancestry. One clear exception they found to the overall pattern of genetic ancestry's effects on immune response being cell-type-specific was in the interferon (IFN, a group of signalling proteins made and released by host cells in response to the presence of several viruses.) response following infection. Across all cell types, increased European ancestry was associated with a stronger type I IFN response shortly after influenza infection, which predicted reduced virus levels at later time points.