Innate Immune Response to Influenza Virus at Single-Cell Resolution in Human Epithelial Cells Revealed Paracrine Induction of Interferon Lambda 1

Journal of Virology
Irene RamosAna Fernandez-Sesma

Abstract

Early interactions of influenza A virus (IAV) with respiratory epithelium might determine the outcome of infection. The study of global cellular innate immune responses often masks multiple aspects of the mechanisms by which populations of cells work as organized and heterogeneous systems to defeat virus infection, and how the virus counteracts these systems. In this study, we experimentally dissected the dynamics of IAV and human epithelial respiratory cell interaction during early infection at the single-cell level. We found that the number of viruses infecting a cell (multiplicity of infection [MOI]) influences the magnitude of virus antagonism of the host innate antiviral response. Infections performed at high MOIs resulted in increased viral gene expression per cell and stronger antagonist effect than infections at low MOIs. In addition, single-cell patterns of expression of interferons (IFN) and IFN-stimulated genes (ISGs) provided important insights into the contributions of the infected and bystander cells to the innate immune responses during infection. Specifically, the expression of multiple ISGs was lower in infected than in bystander cells. In contrast with other IFNs, IFN lambda 1 (IFNL1) showed a widespread patte...Continue Reading

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Citations

Apr 22, 2020·PloS One·John Whitman, Ciriyam Jayaprakash
Aug 14, 2020·PLoS Pathogens·Elizabeth J FayRyan A Langlois
Sep 26, 2020·Frontiers in Immunology·Hanaa Ahmed-HassanNamal P M Liyanage
Jul 8, 2020·Nature Microbiology·Kara L PhippsAnice C Lowen
Oct 28, 2020·Computational and Structural Biotechnology Journal·Geyang LuoBo Yan
Sep 27, 2020·Journal of Virological Methods·Morgan PearsonGregg A Dean
Dec 25, 2019·Cold Spring Harbor Perspectives in Medicine·David J TophamAndrea Sant
May 7, 2021·The Journal of General Virology·Thrimendra Kaushika DissanayakeKelvin Kai-Wang To
Aug 29, 2021·Viruses·Maarit Suomalainen, Urs F Greber
Nov 28, 2021·Viruses·Lily ChanKhalil Karimi

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Datasets Mentioned

BETA
GSE122031

Methods Mentioned

BETA
PCR
single-cell sequencing
chip
Illumina sequencing

Software Mentioned

MatLab scripts
tSNE
Rstudio
Reactome pathway Database
BioRender
Reactome Pathway Database tool
MATLAB
R
Reactome
R package Seurat

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