Abstract
Human cytomegalovirus (HCMV) can result in either productive or non-productive infection, with the latter potentially leading to viral latency. The molecular factors dictating these outcomes are poorly understood. Here we used single-cell transcriptomics to analyse HCMV infection progression in monocytes, which are latently infected, and macrophages, considered to be permissive for productive infection. We show that early viral gene expression levels, specifically of those encoding immediate early proteins IE1 and IE2, are a major factor dictating productive infection. We also revealed that intrinsic, not induced, host cell interferon-stimulated gene expression level is a main determinant of infection outcome. Intrinsic interferon-stimulated gene expression is downregulated with monocyte to macrophage differentiation, partially explaining increased macrophage susceptibility to productive HCMV infection. Furthermore, non-productive macrophages could reactivate, making them potential latent virus reservoirs. Overall, we decipher molecular features underlying HCMV infection outcomes and propose macrophages as a potential HCMV reservoir.
| Original language | English |
|---|---|
| Pages (from-to) | 455-468 |
| Number of pages | 14 |
| Journal | Nature Microbiology |
| Volume | 8 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2023 |
| Externally published | Yes |
Bibliographical note
Funding Information:We thank N. Drayman, R. Winkler and the members of the Stern-Ginossar lab for critical reading of the manuscript. We thank K. Bahar Halpern and S. Ben-Moshe for assistance with mcSCRB-seq and 10x Genomics library preparation. We thank E. A. Murphy for the TB40E-GFP virus strain. We thank the Weizmann flow cytometry unit for technical assistance. This study was supported by a European Research Council consolidator grant to N.S.-G. (CoG-2019-864012). N.S.-G. is a member of the European Molecular Biology Organization (EMBO) Young Investigator Program.
Funding Information:
We thank N. Drayman, R. Winkler and the members of the Stern-Ginossar lab for critical reading of the manuscript. We thank K. Bahar Halpern and S. Ben-Moshe for assistance with mcSCRB-seq and 10x Genomics library preparation. We thank E. A. Murphy for the TB40E-GFP virus strain. We thank the Weizmann flow cytometry unit for technical assistance. This study was supported by a European Research Council consolidator grant to N.S.-G. (CoG-2019-864012). N.S.-G. is a member of the European Molecular Biology Organization (EMBO) Young Investigator Program.
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.