Single cell analysis reveals human cytomegalovirus drives latently infected cells towards an anergic-like monocyte state
- Weizmann Institute of Science, Israel
- University of Cambridge, United Kingdom
- Sydney Cellular Therapies Laboratory, Australia
- University of Sydney, Australia
Abstract
Human cytomegalovirus (HCMV) causes a lifelong infection through establishment of latency. Although reactivation from latency can cause life-threatening disease, our molecular understanding of HCMV latency is incomplete. Here we use single cell RNA-seq analysis to characterize latency in monocytes and hematopoietic stem and progenitor cells (HSPCs). In monocytes, we identify host cell surface markers that enable enrichment of latent cells harboring higher viral transcript levels, which can reactivate more efficiently, and are characterized by reduced intrinsic immune response that is important for viral gene expression. Significantly, in latent HSPCs, viral transcripts could be detected only in monocyte progenitors and were also associated with reduced immune-response. Overall, our work indicates that regardless of the developmental stage in which HCMV infects, HCMV drives hematopoietic cells towards a weaker immune-responsive monocyte state and that this anergic-like state is crucial for the virus ability to express its transcripts and to eventually reactivate.
Data availability
Sequencing data have been deposited in GEO under accession code GSE138838
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Defining the Transcriptional Landscape during Cytomegalovirus Latency with Single-Cell RNA SequencingNCBI Gene Expression Omnibus, GSE101341.
Article and author information
Author details
Noam Stern-Ginossar
Funding
Infect-ERA (TANKACY)
- Noam Stern-Ginossar
H2020 European Research Council (starting grant (StG-2014-638142))
- Noam Stern-Ginossar
Cambridge NIHR BRC Cell Phenotyping Hub
- John Sinclair
British Medical Research Council (G0701279)
- John Sinclair
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Melanie M Brinkmann, Technische Universität Braunschweig, Germany
Ethics
Human subjects: All fresh peripheral blood samples were obtained after approval of protocols bythe Weizmann Institutional Review Board (IRB application 92-1). Informed written consent was obtained from all volunteers, and all experiments were carried out in accordance with the approved guidelines. The study using HSCT recipient samples was approved by the Human Research Ethics Committee of the University of Sydney and the Western Sydney Local Health District. Informed consent was obtained from all study participants prior to enrolment in accordance with the Declaration of Helsinki.
Version history
- Received: September 24, 2019
- Accepted: January 21, 2020
- Accepted Manuscript published: January 22, 2020 (version 1)
- Version of Record published: February 24, 2020 (version 2)
- Version of Record updated: July 16, 2020 (version 3)
Copyright
© 2020, Shnayder et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Single cell analysis reveals human cytomegalovirus drives latently infected cells towards an anergic-like monocyte state
eLife 9:e52168.
https://doi.org/10.7554/eLife.52168
Further reading
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