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Related Experiment Video

Updated: Jul 19, 2025

Infection of Primary Nasal Epithelial Cells Grown at an Air-Liquid Interface to Characterize Human Coronavirus-Host Interactions

Infection of Primary Nasal Epithelial Cells Grown at an Air-Liquid Interface to Characterize Human Coronavirus-Host Interactions

Published on: September 22, 2023

Dissecting human population variation in single-cell responses to SARS-CoV-2.

Yann Aquino^1,2, Aurélie Bisiaux¹, Zhi Li¹

¹Human Evolutionary Genetics Unit, Institut Pasteur, Université Paris Cité, CNRS UMR2000, Paris, France.

|August 9, 2023

Summary

SARS-CoV-2 triggers weaker, more varied immune responses than influenza, with population differences influenced by genetics and cell composition. Natural selection and Neanderthal DNA also shape these diverse immune reactions to viruses.

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Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization

Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization

Published on: December 23, 2020

Area of Science:

Immunology
Genetics
Virology

Background:

Interindividual clinical variability exists after SARS-CoV-2 infection.
Population differences in immune responses to SARS-CoV-2 are not fully understood.

Purpose of the Study:

To investigate population differences in immune responses to SARS-CoV-2 and influenza A virus.
To identify genetic and cellular drivers of these population disparities.

Main Methods:

Single-cell RNA sequencing of peripheral blood mononuclear cells from 222 diverse donors.
Stimulation with SARS-CoV-2 and influenza A virus.
Expression quantitative trait loci and mediation analyses.

Main Results:

SARS-CoV-2 induced weaker, more heterogeneous interferon-stimulated gene activity than influenza A virus.
Marked population differences in transcriptional responses were observed, driven by cell abundance changes.
Natural selection and Neanderthal introgression were found to increase population differences in immune responses.

Conclusions:

Cell composition broadly affects population disparities in immune responses, with genetic variants playing a key role.
Evolutionary factors, including natural selection and archaic introgression, have shaped immune responses to viruses.
Genetic factors underlying immune responses to SARS-CoV-2 overlap with those influencing COVID-19 severity.