4.8 Article

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

Journal

FRONTIERS IN IMMUNOLOGY
Volume 14, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2023.1192057

Keywords

cytomegalovirus; dendritic cells; transcriptome; chemokines; XCL1; XCR1

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Dendritic cells (DC) play a crucial role in antiviral immunity, but can also be infected by Cytomegalovirus (CMV). This study investigates the infection of rat CMV on XCR1+ DC and its effects on cell surface markers and migration behavior. The results show that RCMV infection reduces XCR1 and MHCII surface expression, reverts DC activation, and impairs the chemotactic activity of infected DC.
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+ 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 gamma-chemokine ligand xcl1 (Delta vxcl1 RCMV) infect splenic rat DC ex vivo 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+ 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.

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