Abstract
During productive human cytomegalovirus (HCMV) infection, viral genes are expressed in a coordinated cascade that conventionally relies on the dependencies of viral genes on protein synthesis and viral DNA replication. By contrast, the transcriptional landscape of HCMV latency is poorly understood. Here, we examine viral gene expression dynamics during the establishment of both productive and latent HCMV infections. We redefine HCMV gene expression kinetics during productive infection and reveal that viral gene regulation does not represent a simple sequential cascade; many viral genes are regulated by multiple independent modules. Using our improved gene expression classification combined with transcriptome-wide measurements of the effects of a wide array of epigenetic inhibitors on viral gene expression during latency, we show that a defining feature of latency is the unique repression of immediate-early (IE) genes. Altogether, we recharacterize HCMV gene expression kinetics and reveal governing principles of lytic and latent gene expression.
Original language | English |
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Article number | 110653 |
Journal | Cell Reports |
Volume | 39 |
Issue number | 2 |
DOIs | |
State | Published - 12 Apr 2022 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2022 The Author(s)
Funding
We thank Stern-Ginossar lab members, Oren Kobiler, and Igor Ulitsky for providing valuable feedback. We thank Eain 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 ( CoG-2019-864012 ) and by the Israel Science Foundation ( 1526/18 ). N.S.-G. is a member of the European Molecular Biology Organization ( EMBO ) Young Investigator Program. We thank Stern-Ginossar lab members, Oren Kobiler, and Igor Ulitsky for providing valuable feedback. We thank Eain 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 (CoG-2019-864012) and by the Israel Science Foundation (1526/18). N.S.-G. is a member of the European Molecular Biology Organization (EMBO) Young Investigator Program. B.R. M.S. and N.S.-G. conceived and designed the project. B.R. M.S. R.L.S. and M.L. performed the experiments. B.R. and A.N. prepared figures and performed all bioinformatics and statistical analyses. B.R. M.S. and N.S.-G. wrote the manuscript. All authors had access to the study data and read and approved the final manuscript. The authors declare no competing interests.
Funders | Funder number |
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European Molecular Biology Organization | |
European Commission | CoG-2019-864012 |
Israel Science Foundation | 1526/18 |
Keywords
- CP: Microbiology
- Human cytomegalovirus
- gene expression
- herpesvirus
- latency