PT  - JOURNAL ARTICLE
AU  - Miri Shnayder
AU  - Aharon Nachshon
AU  - Benjamin Krishna
AU  - Emma Poole
AU  - Alina Boshkov
AU  - Amit Binyamin
AU  - Itay Maza
AU  - John Sinclair
AU  - Michal Schwartz
AU  - Noam Stern-Ginossar
TI  - Defining the Transcriptional Landscape during Cytomegalovirus Latency with Single-Cell RNA Sequencing
AID  - 10.1101/208603
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 208603
4099  - http://biorxiv.org/content/early/2017/11/03/208603.short
4100  - http://biorxiv.org/content/early/2017/11/03/208603.full
AB  - Primary infection with human cytomegalovirus (HCMV) results in a lifelong infection due to its ability to establish latent infection, one characterized viral reservoir being hematopoietic cells. Although reactivation from latency causes serious disease in immunocompromised individuals, our molecular understanding of latency is limited. Here, we delineate viral gene expression during natural HCMV persistent infection by analyzing the massive RNA-seq atlas generated by the Genotype-Tissue Expression (GTEx) project. This systematic analysis reveals that HCMV persistence in-vivo is prevalent in diverse tissues. Unexpectedly, we find only viral transcripts that resemble gene expression during stages of lytic infection with no evidence of any highly restricted latency-associated viral gene expression program. To further define the transcriptional landscape during HCMV latent infection, we also used single cell RNA-seq and a tractable experimental latency model. In contrast to current views on latency, we also find no evidence for a specific restricted latency-associated viral gene expression program. Instead, we reveal that latency-associated gene expression largely mirrors a late lytic viral program albeit at much lower levels of expression. Overall, our work has the potential to revolutionize our understanding of HCMV persistence and suggests that latency is governed mainly by quantitative changes, with a limited number of qualitative changes, in viral gene expression.