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 Islands, Asia, and South/Central America. Many steps of the replication and expression of CHIKV's 12-kb
RNA genome are highly dependent on cellular factors, which thus constitute potential therapeutic targets. SILAC and LC-MS/MS were used to define the temporal dynamics of the cellular response to
infection. Using samples harvested at 8, 10, and 12 h postinfection, over 4700
proteins were identified and per time point 2800-3500
proteins could be quantified in both
biological replicates. At 8, 10, and 12 h postinfection, 13, 38, and 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), and
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).