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Cell Syst. 2018 Jun 27;6(6):679-691.e4. doi: 10.1016/j.cels.2018.05.008. Epub 2018 Jun 6.

Dissection of Influenza Infection In Vivo by Single-Cell RNA Sequencing.

Author information

1
School of Molecular Cell Biology and Biotechnology, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 6997801 Tel Aviv, Israel.
2
Department of Immunology, The Weizmann Institute of Science, 7610001 Rehovot, Israel.
3
Department of Immunology, The Weizmann Institute of Science, 7610001 Rehovot, Israel. Electronic address: ido.amit@weizmann.ac.il.
4
School of Molecular Cell Biology and Biotechnology, Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 6997801 Tel Aviv, Israel. Electronic address: iritgv@post.tau.ac.il.

Abstract

The influenza virus is a major cause of morbidity and mortality worldwide. Yet, both the impact of intracellular viral replication and the variation in host response across different cell types remain uncharacterized. Here we used single-cell RNA sequencing to investigate the heterogeneity in the response of lung tissue cells to in vivo influenza infection. Analysis of viral and host transcriptomes in the same single cell enabled us to resolve the cellular heterogeneity of bystander (exposed but uninfected) as compared with infected cells. We reveal that all major immune and non-immune cell types manifest substantial fractions of infected cells, albeit at low viral transcriptome loads relative to epithelial cells. We show that all cell types respond primarily with a robust generic transcriptional response, and we demonstrate novel markers specific for influenza-infected as opposed to bystander cells. These findings open new avenues for targeted therapy aimed exclusively at infected cells.

KEYWORDS:

bystander versus infected cells; immune and non-immune cell types; influenza infection in vivo; single-cell RNA sequencing

PMID:
29886109
DOI:
10.1016/j.cels.2018.05.008

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