Highly Multiplexed Proteomic Analysis of HCMV Infected Dendritic Cells Reveals Global Manipulation of Adaptive Immunity and Host Restriction of Viral Replication
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HCMV is a clinically significant herpesvirus and a paradigm for pathogen-mediated immune-evasion. Its broad tropism includes antigen-presenting cells such as dendritic cells (DCs), which may partly explain a unique, dramatic imprint on host immunity that occurs following lifelong carriage. Despite this, most studies use fibroblasts as a model. We therefore developed systems to isolate pure populations of DCs following infection with wild-type HCMV, before applying our quantitative temporal proteomic technologies to systematically characterise the virus:DC interaction within cells and at the cell surface. This comprehensive dataset quantifying almost 9,000 proteins throughout the infection timecourse revealed multiple DC-specific viral:host effects, including key impacts on innate, intrinsic, and adaptive immunity. These included observations that APOBEC3A is downregulated in infected cells and restricts HCMV infection in ex vivo DCs, delaying the progression of lytic infection, and that cell surface ICOS-Ligand was downregulated by two viral genes, inhibiting the induction of adaptive immunity.