%0 Journal Article %1 Costa2024 %A Costa, B %A Becker, J %A Krammer, T %A Mulenge, F %A Duran, V %A Pavlou, A %A Gern, O L %A Chu, X %A Li, Y %A Cicin-Sain, L %A Eiz-Vesper, B %A Messerle, M %A Dölken, L %A Saliba, AE %A Erhard, F %A Kalinke, U %D 2024 %J Nat Commun %K kalinke %N 1 %P 1745 %R 10.1038/s41467-024-45614-3 %T Human cytomegalovirus exploits STING signaling and counteracts IFN/ISG induction to facilitate infection of dendritic cells %U https://pubmed.ncbi.nlm.nih.gov/38409141/ %V 15 %X 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.