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Title: Comprehensive proteomic analysis of white blood cells from chikungunya fever patients of different severities
Authors: Nitwara Wikan
Sarawut Khongwichit
Weerawat Phuklia
Sukathida Ubol
Tipparat Thonsakulprasert
Montri Thannagith
Duangrudee Tanramluk
Atchara Paemanee
Suthathip Kittisenachai
Sittiruk Roytrakul
Smith, Duncan R
Mahidol University. Institute of Molecular Biosciences
Mahidol University. Center for Emerging and Neglected Infectious Diseases
Keywords: Chikungunya;Proteome;Inflammasome;Caspase 1;Open Access article
Issue Date: 2014
Citation: Journal of Translational Medicine. Vol. 12, No.96 (2014), 1-8
Abstract: Background: Chikungunya 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. Methods: White 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. Results: CHIKV 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. Conclusions: This 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.
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