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Single cell analysis reveals human cytomegalovirus drives latently infected cells towards an anergic-like monocyte state

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Shnayder, Miri 
Nachshon, Aharon 
Rozman, Batsheva 
Bernshtein, Biana 
Lavi, Michael 


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.



Research Article, Microbiology and Infectious Disease, cytomegalovirus, herpesvirus, latency, single-cell RNA-seq, reactivation, hematopoietic stem and progenitor cells, Human

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eLife Sciences Publications, Ltd
Seventh Framework Programme (Infect-ERA, TANKACY)
H2020 European Research Council (Starting grant (StG-2014-638142))
National Institute for Health Research (Cambridge NIHR BRC Cell Phenotyping Hub)
Medical Research Council (G0701279)