Summary

Humans differ in their susceptibility to infectious disease, partly owing to variation in the immune response after infection. We used single-cell RNA sequencing to quantify variation in the response to influenza infection in peripheral blood mononuclear cells from European- and African-ancestry males. Genetic ancestry effects are common but highly cell type specific. Higher levels of European ancestry are associated with increased type I interferon pathway activity in early infection, which predicts reduced viral titers at later time points. Substantial population-associated variation is explained by cis-expression quantitative trait loci that are differentiated by genetic ancestry. Furthermore, genetic ancestry–associated genes are enriched among genes correlated with COVID-19 disease severity, suggesting that the early immune response contributes to ancestry-associated differences for multiple viral infection outcomes.

Overall design

Multiplexed single-cell RNA expression profiles of control (mock-infected) and influenza A virus (IAV)-infected peripheral blood mononuclear cells (PBMCs) collected from African and European American individuals

Contributors

Haley E. Randolph†, Luis B. Barreiro✉️

Contact

To be supplemented.