Quantitative Proteomics Analysis of Lytic KSHV Infection in Human Endothelial Cells Reveals Targets of Viral Immune Modulation.
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Gabaev, I., Williamson, J., Crozier, T., Schulz, T. F., & Lehner, P. (2020). Quantitative Proteomics Analysis of Lytic KSHV Infection in Human Endothelial Cells Reveals Targets of Viral Immune Modulation.. Cell Rep, 33 (2), 108249. https://doi.org/10.1016/j.celrep.2020.108249
Kaposi's sarcoma herpesvirus (KSHV) is an oncogenic human virus and the leading cause of mortality in HIV infection. KSHV reactivation from latent- to lytic-stage infection initiates a cascade of viral gene expression. Here we show how these changes remodel the host cell proteome to enable viral replication. By undertaking a systematic and unbiased analysis of changes to the endothelial cell proteome following KSHV reactivation, we quantify >7,000 cellular proteins and 71 viral proteins and provide a temporal profile of protein changes during the course of lytic KSHV infection. Lytic KSHV induces >2-fold downregulation of 291 cellular proteins, including PKR, the key cellular sensor of double-stranded RNA. Despite the multiple episomes per cell, CRISPR-Cas9 efficiently targets KSHV genomes. A complementary KSHV genome-wide CRISPR genetic screen identifies K5 as the viral gene responsible for the downregulation of two KSHV targets, Nectin-2 and CD155, ligands of the NK cell DNAM-1 receptor.
Cell Line, Endothelial Cells, Humans, Herpesvirus 8, Human, Sarcoma, Kaposi, DNA-Directed DNA Polymerase, eIF-2 Kinase, Proteome, Viral Proteins, Antigens, Differentiation, T-Lymphocyte, Ligands, Proteomics, Virus Activation, Down-Regulation, Up-Regulation, Kinetics, Mutation, Gene Library, Genes, Viral, Genetic Testing, Immunomodulation, Gene Ontology
Horizon 2020/grant agreement no. 656511 Deutsche Forschungsgemeinschaft – SFB900/3 – 158989968; project C1.
European Commission (656511)
Medical Research Council (MR/R001405/1)
Embargo Lift Date
External DOI: https://doi.org/10.1016/j.celrep.2020.108249
This record's URL: https://www.repository.cam.ac.uk/handle/1810/310646
Attribution 4.0 International (CC BY)
Licence URL: http://creativecommons.org/licenses/by/4.0/