Human cytomegalovirus (HCMV) is a widespread pathogen establishing a latent infection in its host. HCMV reactivation is a major health burden in immunocompromised individuals, and is a major cause of morbidity and mortality following hematopoietic stem cell transplantation (HSCT). Here we determined HCMV genomic levels using droplet digital PCR in different peripheral blood mononuclear cell (PBMC) populations in HCMV reactivating HSCT patients. This high sensitivity approach revealed that all PBMC populations harbored extremely low levels of viral DNA at the peak of HCMV DNAemia. Transcriptomic analysis of PBMCs from high-DNAemia samples revealed elevated expression of genes typical of HCMV specific T cells, while regulatory T cell enhancers as well as additional genes related to immune response were downregulated. Viral transcript levels in these samples were extremely low, but remarkably, the detected transcripts were mainly immediate early viral genes. Overall, our data indicate that HCMV DNAemia is associated with distinct signatures of immune response in the blood compartment, however it is not necessarily accompanied by substantial infection of PBMCs and the residual infected PBMCs are not productively infected.

人类巨细胞病毒（HCMV）是一种广泛的病原体，在其宿主中建立潜伏感染。HCMV激活是免疫受损个体的主要健康负担，并且是造血干细胞移植（HSCT）后发病和死亡的主要原因。在这里，我们在HCMV激活HSCT患者的不同外周血单核细胞（PBMC）群体中使用液滴数字PCR确定了HCMV基因组水平。这种高敏感性方法表明，所有PBMC群体在HCMV DNAemia高峰期都携带极低水平的病毒DNA。对来自高DNAemia样本的PBMC的转录组学分析显示，HCMV特异性T细胞典型基因的表达升高，而调节性T细胞增强子以及与免疫反应相关的其他基因被下调。这些样品中的病毒转录物水平极低，但是值得注意的是，检测到的转录物主要是立即的早期病毒基因。总的来说，我们的数据表明，HCMV DNAemia与血液腔室中免疫反应的明显特征有关，但是不一定伴随着PBMC的大量感染，而残留的感染PBMC并未受到生产性感染。