Differential Proteome Analysis of Chikungunya Virus Infection on Host Cells

Abstract

BackgroundChikungunya virus (CHIKV) is an emerging mosquito-borne alphavirus that has caused multiple unprecedented and re-emerging outbreaks in both tropical and temperate countries. Despite ongoing research efforts, the underlying factors involved in facilitating CHIKV replication during early infection remains ill-characterized. The present study serves to identify host proteins modulated in response to early CHIKV infection using a proteomics approach.Methodology and Principal FindingsThe whole cell proteome profiles of CHIKV-infected and mock control WRL-68 cells were compared and analyzed using two-dimensional gel electrophoresis (2-DGE). Fifty-three spots were found to be differentially modulated and 50 were successfully identified by MALDI-TOF/TOF. Eight were significantly up-regulated and 42 were down-regulated. The mRNA expressions of 15 genes were also found to correlate with the corresponding protein expression. STRING network analysis identified several biological processes to be affected, including mRNA processing, translation, energy production and cellular metabolism, ubiquitin-proteasome pathway (UPP) and cell cycle regulation.Conclusion/SignificanceThis study constitutes a first attempt to investigate alteration of the host cellular proteome during early CHIKV infection. Our proteomics data showed that during early infection, CHIKV affected the expression of proteins that are involved in mRNA processing, host metabolic machinery, UPP, and cyclin-dependent kinase 1 (CDK1) regulation (in favour of virus survival, replication and transmission). While results from this study complement the proteomics results obtained from previous late host response studies, functional characterization of these proteins is warranted to reinforce our understanding of their roles during early CHIKV infection in humans.

Global protein profiling studies of chikungunya virus infection identify different proteins but common biological processes

“…Abere and colleagues looked at the changes in CHIKV infected CHME‐5 microglial cells initially by 2D electrophoresis and observed some 59 altered spots, a number consistent with the 53 differentially regulated protein spots seen by Thio and colleagues who investigated the changes in CHIKV infected WRL‐68 cells. Although Thio and colleagues moved directly to the analysis of the protein spots through matrix‐assisted laser desorption/ionization‐tandem time‐of‐flight (MALDI‐TOF/TOF), Abere and colleagues undertook subsequent analysis through GeLC‐MS/MS and identified some 90 significant differentially regulated proteins. Thio and colleagues successfully identified 50 of the spots, which mapped to 45 distinct proteins as shown in Table 1 of their study .…”

“… Studies are identified by the first name of the author and where required, the year (Thio ; Abere ; Dhanwani (2011) ; Dhanwani (2014) ; ; Fraisier ; Wikan ; Puttamallesh ) and the protein ID or accession number listed in the study is given. Where required the proteome (liver or brain) or technique (DIGE or iTRAQ) is also indicated.…”

“…Combined, the seven studies reported nine proteomic analyses and documented collectively more than 700 proteins differentially regulated by CHIKV infection . Combining all of the unambiguous protein information from all of the studies, only 26 proteins (Table ) were detected in more than one analysis.…”

Differential Analysis of the Secretome of WRL68 Cells Infected with the Chikungunya Virus

“…The search parameters used were as previously described [5]. Proteins were represented as nodes and their functional links were defined by solid lines.…”

Antiviral responses of arthropod vectors: an update on recent advances

“…Recent advances in high throughput technologies, such as transcriptomics and proteomics, for pathogen-host interaction studies [25,52,96,109,117,136], as well as the publication of several vector species genomes including the mosquitoes Culex quinquefasciatus [2], Anopheles gambiae [49] and Aedes aegypti [89] and the tick Ixodes scapularis [46], have led to the discovery of immunity pathway orthologues in these species [65,105]. While there is no midge genome available to date, recent combined efforts of The Pirbright Institute and the European Bioinformatics Institute (part of the European Molecular Biology Laboratory; EBI-EMBL) have led to the first full de novo sequencing project for Culicoides sonorensis.…”