Comprehensive proteomic analysis of white blood cells from chikungunya fever patients of different severities
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 dise...
Saved in:
Main Authors: | , , , , , , , , , , |
---|---|
Other Authors: | |
Format: | Article |
Language: | English |
Published: |
2015
|
Subjects: | |
Online Access: | https://repository.li.mahidol.ac.th/handle/123456789/1813 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Mahidol University |
Language: | English |
Summary: | 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. |
---|