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.
Highlights
Chikungunya (CHIK) is a long-neglected disease that only recently began to garner attention from the scientific community following devastating outbreaks that struck India and the Indian Ocean Islands from 2004 to 2007
Contrary to the aforementioned proteomics research which investigated the late host response to Chikungunya virus (CHIKV) infection [13], our present study aims to identify proteins altered during early infection in the host cells by means of 2-dimensional gel electrophoresis (2-DGE)
Cytopathogenicity of CHIKV The cytopathic nature of CHIKV infection in mammalian cell lines, which was reported in several studies [9,15,16], was observed in WRL-68 cells infected with the virus at varying MOI (MOI of 0.5, 1.0, 5.0 and 10.0) and time-points (24 and 48 h)
Summary
Chikungunya (CHIK) is a long-neglected disease that only recently began to garner attention from the scientific community following devastating outbreaks that struck India and the Indian Ocean Islands from 2004 to 2007. This disease causes substantial morbidity and an estimated death rate of 1:1,000 [1]. The causative agent for CHIK infection is the chikungunya virus (CHIKV), an alphavirus belonging to the family Togaviridae [6]. Chikungunya virus (CHIKV) is an emerging mosquito-borne alphavirus that has caused multiple unprecedented and re-emerging outbreaks in both tropical and temperate countries. The present study serves to identify host proteins modulated in response to early CHIKV infection using a proteomics approach
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