AUTHOR=Madela-Mönchinger Julia Cecilia , Wolf Silver Anthony , Wyler Emanuel , Bauer Agnieszka , Mischke Marius , Möller Lars , Juranić Lisnić Vanda , Landthaler Markus , Malyshkina Anna , Voigt Sebastian 

TITLE=Rat cytomegalovirus efficiently replicates in dendritic cells and induces changes in their transcriptional profile

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1192057

DOI=10.3389/fimmu.2023.1192057

ISSN=1664-3224

ABSTRACT=<p>Dendritic cells (DC) play a crucial role in generating and maintaining antiviral immunity. While DC are implicated in the antiviral defense by inducing T cell responses, they can also become infected by Cytomegalovirus (CMV). CMV is not only highly species-specific but also specialized in evading immune protection, and this specialization is in part due to characteristic genes encoded by a given virus. Here, we investigated whether rat CMV can infect XCR1<sup>+</sup> DC and if infection of DC alters expression of cell surface markers and migration behavior. We demonstrate that wild-type RCMV and a mutant virus lacking the γ-chemokine ligand <italic>xcl1</italic> (<italic>Δvxcl1</italic> RCMV<italic>)</italic> infect splenic rat DC <italic>ex vivo</italic> and identify viral assembly compartments. Replication-competent RCMV reduced XCR1 and MHCII surface expression. Further, gene expression of infected DC was analyzed by bulk RNA-sequencing (RNA-Seq). RCMV infection reverted a state of DC activation that was induced by DC cultivation. On the functional level, we observed impaired chemotactic activity of infected XCR1<sup>+</sup> DC compared to mock-treated cells. We therefore speculate that as a result of RCMV infection, DC exhibit diminished XCR1 expression and are thereby blocked from the lymphocyte crosstalk.</p>