A new study to explain differential susceptibility to viral outbreaks reveals that ancestry and associated genetic variation may explain population-level differences in the immune response to influenza virus and possibly COVID-19 as well.
Viruses are among the strongest sources of selection pressure in human evolution. However, before the modern era, generalized pandemics were probably rare. Instead, virus outbreaks have been confined to regional populations. Thus, if past viral outbreaks were geographically contained, they could have resulted in population divergence in responses to viral infection in pockets. While ancestry has been associated with differences in responses to viruses, the molecular determinants of these variations remain unclear.
Here, to quantify the variation in response to influenza infection, Haley Randolph and colleagues used single-cell RNA sequencing of peripheral blood mononuclear cells infected with influenza A virus. in vitro individuals of European and African genetic descent. According to Randolph et al.The infection led to gene signatures that diverged in a cell type specific way, correlating with ancestry. One clear exception they found to the overall pattern of the effects of genetic ancestry on the cell-type-specific immune response was the response to interferon (IFN) after infection. In all cell types, increased European ancestry was associated with a stronger IFN type I response soon after influenza infection, which in turn predicted reduced virus levels at later times.
“Given the central role played by IFNs in conferring antiviral activity on host cells, our results have potential clinical implications not only for influenza infection but also for other viruses, including SARS-CoV-2, for which timing and magnitude of IFN-mediated antiviral responses are associated with disease progression and severity, say the authors.
The study also showed that genes expressed differently based on genetic ancestry are involved in responses to other single-stranded RNA viruses, including SARS-CoV-2 – a finding that could contribute to the differences observed. between susceptibility to COVID-19 between African Americans and Europeans. Americans.
American Association for the Advancement of Science (AAAS)
Randolph, SE, et al. (2021) The effects of genetic ancestry on the response to viral infection are ubiquitous but cell type specific. Science. doi.org/10.1126/science.abg0928.