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- W340293171 abstract "Chikungunya virus (CHIKV) is an arthropod-borne virus that has causedmultiple unprecedented outbreaks in both tropical and temperate countries over the pastfive decades. There is no commercial vaccine or antiviral drug to date, due in part tothe lack of knowledge and understanding of the biology and pathogenesis of this virus.Thus, there is an increasing need for researchers to focus their research efforts in thisarea of virology. The current study employed proteomics to investigate alterations ofthe whole cell proteome and secretome of WRL-68 cells during early CHIKV infection,with the main aim being to identify the key proteins modulated in response to infection.Two-dimensional gel electrophoresis (2-DGE) was used to compare the whole cellproteome and secretome profiles between mock control cells and cells infected at theoptimised multiplicity of infection (MOI) of 5.0 at 24 hours post-infection. Proteinspots that were found to be differentially expressed were identified by MALDITOF/TOF mass spectrometry (MS) analysis, and three selected proteins were validatedby Western blot. The functional association between these proteins were determined bySTRING network analysis, and the mRNA expression level of selected proteins wasinvestigated via real-time quantitative PCR. Overall, 50 and 25 protein spots from thewhole cell proteome and secretome samples, respectively, were found to bedifferentially expressed (fold-change > 1.3, p < 0.05) and were successfully identified.The mRNA expression of 15 whole cell proteins was found to correlate with thecorresponding protein expression. On the contrary, only one of the 15 selected proteinsfrom the secretome sample showed positive correlation with its transcript expressionlevel. By combining the proteomics and bioinformatics data from STRING networkanalysis, it was deduced that CHIKV disrupt the overall host cell metabolic machineryand ubiquitin-proteasome pathway (UPP). Suppression of the host immune responsewas also observed through the inhibition of immune-related protein secretion, mainlyiicathepsin D, cathepsin L1, C3 protein and β-2 microglobulin. Several gene expressionrelatedproteins were also down-regulated, including the mRNA processing factor,hnRNP E1, and translational factors, namely elongation factor-2, eukaryotic initiationfactor eIF-2BA and eIF3 subunit H. Meanwhile, up-regulation of hnRNP C1/C2suggests that this protein may be beneficial to CHIKV. Cell cycle regulation via cyclindependentkinase 1 (CDK1) activity may also play an important role during earlyCHIKV infection. CDK1 was down-regulated, whereas several other proteins (such asSET protein) that indirectly regulate the activity of CDK1, were altered in favour of theinhibition of CDK1 activity. In conclusion, CHIKV infection in the human liver cellsinduced a widespread alteration of the whole cell proteome and secretome.Nevertheless functional characterisations of these proteins are entailed to provide moreinsights into the actual mechanisms at play during early infection." @default.
- W340293171 created "2016-06-24" @default.
- W340293171 creator A5089133908 @default.
- W340293171 date "2013-01-01" @default.
- W340293171 modified "2023-09-24" @default.
- W340293171 title "Proteomic analysis on host responses to Chikungunya virus infection / Christina Thio Li Ping" @default.
- W340293171 hasPublicationYear "2013" @default.
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