Temporal SILAC-based quantitative proteomics identifies host factors involved in Chikungunya virus replication
Autor(es): Treffers Emmely E, Tas Ali, Scholte Florine E M, Van Myrthe N, Heemskerk Matthias T, de Ru Arnoud H, Snijder Eric J, van Hemert Martijn J, van Veelen Peter A
Resumo: Chikungunya virus (CHIKV) is an arthropod-borne reemerging human pathogen that generally causes a severe persisting arthritis. Since 2005, the virus has infected millions of people during outbreaks in Africa, Indian Ocean Isl-s, Asia, - South/Central America. Many steps of the replication - expression of CHIKV's 12-kb RNA genome are highly dependent on cellular factors, which thus constitute potential therapeutic targets. SILAC - LC-MS/MS were used to define the temporal dynamics of the cellular response to infection. Using samples harvested at 8, 10, - 12 h postinfection, over 4700 proteins were identified - per time point 2800-3500 proteins could be quantified in both biological replicates. At 8, 10, - 12 h postinfection, 13, 38, - 106 proteins, respectively, were differentially expressed. The majority of these proteins showed decreased abundance. Most subunits of the RNA polymerase II complex were progressively degraded, which likely contributes to the transcriptional host shut-off observed during CHIKV infection. Overexpression of four proteins that were significantly downregulated (Rho family GTPase 3 (Rnd3), DEAD box helicase 56 (DDX56), polo-like kinase 1 (Plk1), - ubiquitin-conjugating enzyme E2C (UbcH10) reduced susceptibility of cells to CHIKV infection, suggesting that infection-induced downregulation of these proteins is beneficial for CHIKV replication. All MS data have been deposited in the ProteomeXchange with identifier PXD001330 (http://proteomecentral.proteomexchange.org/dataset/PXD001330).
Palavras-Chave: Alphavirus; Chikungunya virus; Microbiology; SILAC; Temporal proteomics; Virus-host interactions
Imprenta: Proteomics, v. 15, n. 13, p. 2267-2280, 2015
Identificador do objeto digital: 10.1002/pmic.201400581
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Genome ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya Virus - Virus
Data de publicação: 2015
