Single-Cell Virus Sequencing of Influenza Infections That Trigger Innate Immunity.
10x Chromium
NS1
PB1
PacBio
defective virus
heterogeneity
influenza virus
interferon
single-cell RNA-seq
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
15 07 2019
15 07 2019
Historique:
received:
24
03
2019
accepted:
29
04
2019
pubmed:
10
5
2019
medline:
27
5
2020
entrez:
10
5
2019
Statut:
epublish
Résumé
Influenza virus-infected cells vary widely in their expression of viral genes and only occasionally activate innate immunity. Here, we develop a new method to assess how the genetic variation in viral populations contributes to this heterogeneity. We do this by determining the transcriptome and full-length sequences of all viral genes in single cells infected with a nominally "pure" stock of influenza virus. Most cells are infected by virions with defects, some of which increase the frequency of innate-immune activation. These immunostimulatory defects are diverse and include mutations that perturb the function of the viral polymerase protein PB1, large internal deletions in viral genes, and failure to express the virus's interferon antagonist NS1. However, immune activation remains stochastic in cells infected by virions with these defects and occasionally is triggered even by virions that express unmutated copies of all genes. Our work shows that the diverse spectrum of defects in influenza virus populations contributes to-but does not completely explain-the heterogeneity in viral gene expression and immune activation in single infected cells.
Identifiants
pubmed: 31068418
pii: JVI.00500-19
doi: 10.1128/JVI.00500-19
pmc: PMC6600203
pii:
doi:
Substances chimiques
INS1 protein, influenza virus
0
Viral Nonstructural Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : Wellcome Trust
ID : 206579/Z/17/Z
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI127893
Pays : United States
Organisme : NIH HHS
ID : S10 OD020069
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
Copyright © 2019 Russell et al.
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