Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
Elife. 2020 Jan 22;9:e52168. doi: 10.7554/eLife.52168.
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.
人巨细胞病毒（HCMV）通过建立潜伏感染而导致终身感染。尽管从潜伏中重新激活可能导致危及生命的疾病，但我们对 HCMV 潜伏的分子理解还不完全。在这里，我们使用单细胞 RNA-seq 分析来描述单核细胞和造血干细胞和祖细胞（HSPCs）中的潜伏。在单核细胞中，我们鉴定了宿主细胞表面标记物，这些标记物可以富集潜伏细胞，这些细胞具有更高的病毒转录本水平，可以更有效地重新激活，并且其固有免疫反应降低，这对病毒基因表达很重要。重要的是，在潜伏的 HSPCs 中，仅在单核细胞祖细胞中可以检测到病毒转录本，并且也与降低的免疫反应相关。总体而言，我们的工作表明，无论 HCMV 感染的发育阶段如何，HCMV 都会促使造血细胞向免疫反应较弱的单核细胞状态发展，这种无反应状态对于病毒表达其转录本并最终重新激活的能力至关重要。
