Quantitative proteomics defines mechanisms of antiviral defence and cell death during modified vaccinia Ankara infection

Journal article

Human cytomegalovirus (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 breadth of infection, most studies use fibroblasts as a model. We therefore developed systems to isolate pure populations of DCs infected with wild-type HCMV, before applying 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 effects included observations that APOBEC3A is downregulated in infected cells and restricts HCMV infection in<jats:italic>ex vivo</jats:italic>DCs, delaying the progression of lytic infection, and that cell surface ICOS-Ligand was downregulated by the viral genes US16 and US20, inhibiting the induction of adaptive immunity

Authors: Albarnaz, JD; Kite, J; Oliveira, M; Li, H; Di, Y

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Communications
• Volume: 14
• Issue: 1
• Pages: 8134-8134
• Article number: 8134
• Publication date: 2023-12-08
• DOI: 10.1038/s41467-023-43299-8
• EISSN: 2041-1723
• ISSN: 2041-1723
• Language: English
• Keywords: Proteomics; Inflammation; Immunology; Interferon; Viral replication; Gene; Recombinant DNA; Virology; Computational biology; Innate immune system; Modified vaccinia Ankara; Biology; Virus; Proteome; Effector; Vaccinia; Immune system; Cell biology; Quantitative proteomics; Inflammasome; Genetics