Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Centre for Infection Research (HZI), Würzburg, Germany.
Nat Commun. 2024 Feb 26;15(1):1745. doi: 10.1038/s41467-024-45614-3.
Human cytomegalovirus (HCMV) is a widespread pathogen that in immunocompromised hosts can cause life-threatening disease. Studying HCMV-exposed monocyte-derived dendritic cells by single-cell RNA sequencing, we observe that most cells are entered by the virus, whereas less than 30% of them initiate viral gene expression. Increased viral gene expression is associated with activation of the stimulator of interferon genes (STING) that usually induces anti-viral interferon responses, and with the induction of several pro- (RHOB, HSP1A1, DNAJB1) and anti-viral (RNF213, TNFSF10, IFI16) genes. Upon progression of infection, interferon-beta but not interferon-lambda transcription is inhibited. Similarly, interferon-stimulated gene expression is initially induced and then shut off, thus further promoting productive infection. Monocyte-derived dendritic cells are composed of 3 subsets, with one being especially susceptible to HCMV. In conclusion, HCMV permissiveness of monocyte-derived dendritic cells depends on complex interactions between virus sensing, regulation of the interferon response, and viral gene expression.
人类巨细胞病毒（HCMV）是一种广泛存在的病原体，在免疫功能低下的宿主中可导致危及生命的疾病。通过单细胞 RNA 测序研究 HCMV 暴露的单核细胞衍生树突状细胞，我们观察到大多数细胞被病毒进入，而只有不到 30%的细胞启动病毒基因表达。病毒基因表达的增加与干扰素基因刺激物（STING）的激活有关，STING 通常会诱导抗病毒干扰素反应，并诱导几种促病毒（RHOB、HSP1A1、DNAJB1）和抗病毒（RNF213、TNFSF10、IFI16）基因的表达。随着感染的进展，干扰素-β而不是干扰素-λ的转录受到抑制。同样，干扰素刺激基因的表达最初被诱导，然后被关闭，从而进一步促进了有效的感染。单核细胞衍生的树突状细胞由 3 个亚群组成，其中一个亚群特别容易受到 HCMV 的影响。总之，单核细胞衍生的树突状细胞对 HCMV 的易感性取决于病毒感应、干扰素反应调节和病毒基因表达之间的复杂相互作用。
