Comprehensive proteomic analysis of white blood cells from chikungunya fever patients of different severities

Abstract

BackgroundChikungunya fever (CHIKF) is a recently re-emerged mosquito transmitted viral disease caused by the chikungunya virus (CHIKV), an Alphavirus belonging to the family Togaviridae. Infection of humans with CHIKV can result in CHIKF of variable severity, although the factors mediating disease severity remain poorly defined.MethodsWhite blood cells were isolated from blood samples collected during the 2009-2010 CHIKF outbreak in Thailand. Clinical presentation and viral load data were used to classify samples into three groups, namely non chikungunya fever (non-CHIKF), mild CHIKF, and severe CHIKF. Five samples from each group were analyzed for protein expression by GeLC-MS/MS.ResultsCHIKV proteins (structural and non-structural) were found only in CHIKF samples. A total of 3505 human proteins were identified, with 68 proteins only present in non-CHIKF samples. A total of 240 proteins were found only in CHIKF samples, of which 65 and 46 were found only in mild and severe CHIKF samples respectively. Proteins with altered expression mapped predominantly to cellular signaling pathways (including toll-like receptor and PI3K-Akt signaling) although many other processes showed altered expression as a result of CHIKV infection. Expression of proteins consistent with the activation of the inflammasome was detected, and quantitation of (pro)-caspase 1 at the protein and RNA levels showed an association with disease severity.ConclusionsThis study confirms the infection of at least a component of white blood cells by CHIKV, and shows that CHIKV infection results in activation of the inflammasome in a manner that is associated with disease severity.

Evidence of plasticity in the dengue virus: Host cell interaction

“…A total of 2 mg of the sub-10 kDa protein fraction were reduced with DTT, alkylated with Iodoacetamide, digested with trypsin and subjected to LC-MS/MS analysis exactly as described previously [27]. The resultant mass spectra were analyzed with the DeCyder MS Differential Analysis software and the MS/MS data were submitted for a database search using the Mascot software (Matrix Science, London, UK).…”

Inflammasome control of viral infection

“…On the other hand, increased expression of NLRP3 in human patients was observed during infection with chikungunya virus (CHIKV) and elevated caspase-1 expression and IL-1β levels were highly predictive markers of severe disease in humans [63,64]. Dengue virus (DV) also activates the NLRP3 inflammasome in human platelets that were experimentally infected or in platelets isolated from DV infected patients and high platelet derived IL-1β levels caused increased permeability in an in vitro assay and were associated with increased vascular permeability in clinical cases [65].…”

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

“… 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.…”