Cell type-specific HCMV gene expression and its consequences for the MHC-I immunopeptidome

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Systems biology approaches uncovered hundreds of translated open reading frames and thousands of transcription initiation sites in the genome of human cytomegalovirus (HCMV). Previous studies focused on fibroblasts as model system. There is, however, evidence that HCMV gene expression differs substantially among infected cell types. We will uncover the cell type-specific HCMV transcriptome and translatome and will elucidate how HCMV usurps cellular and viral factors to adapt viral gene expression to the different metabolic and immunological conditions within different cell types during lytic infection. We will test the hypotheses that switches from non-productive transcription of transient RNAs to productive transcription of stable RNAs define the cell type-specific and time dependent transcriptome of HCMV and that uORFs fine-tune the translation of proteins. We will furthermore develop mathematical models to integrate expression data and quantitative MHC-I ligandome data to investigate how the kinetics of gene expression is related to MHC-I peptide presentation for both cellular and viral antigens. In collaboration with the other members of our RU we will use our findings to identify and validate novel targets for diagnostic, prophylactic or therapeutic approaches to combat HCMV infections.