Single-cell genome-wide association reveals that a nonsynonymous variant in ERAP1 confers increased susceptibility to influenza virus.

Journal Article (Journal Article)

During pandemics, individuals exhibit differences in risk and clinical outcomes. Here, we developed single-cell high-throughput human in vitro susceptibility testing (scHi-HOST), a method for rapidly identifying genetic variants that confer resistance and susceptibility. We applied this method to influenza A virus (IAV), the cause of four pandemics since the start of the 20th century. scHi-HOST leverages single-cell RNA sequencing (scRNA-seq) to simultaneously assign genetic identity to cells in mixed infections of cell lines of European, African, and Asian origin, reveal associated genetic variants for viral burden, and identify expression quantitative trait loci. Integration of scHi-HOST with human challenge and experimental validation demonstrated that a missense variant in endoplasmic reticulum aminopeptidase 1 (ERAP1; rs27895) increased IAV burden in cells and human volunteers. rs27895 exhibits population differentiation, likely contributing to greater permissivity of cells from African populations to IAV. scHi-HOST is a broadly applicable method and resource for decoding infectious-disease genetics.

Full Text

Duke Authors

Cited Authors

  • Schott, BH; Wang, L; Zhu, X; Harding, AT; Ko, ER; Bourgeois, JS; Washington, EJ; Burke, TW; Anderson, J; Bergstrom, E; Gardener, Z; Paterson, S; Brennan, RG; Chiu, C; McClain, MT; Woods, CW; Gregory, SG; Heaton, NS; Ko, DC

Published Date

  • November 9, 2022

Published In

Volume / Issue

  • 2 / 11

PubMed ID

  • 36465279

Pubmed Central ID

  • PMC9718543

Electronic International Standard Serial Number (EISSN)

  • 2666-979X

Digital Object Identifier (DOI)

  • 10.1016/j.xgen.2022.100207


  • eng

Conference Location

  • United States