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.
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.
Authors: G Rezza; L Nicoletti; R Angelini; R Romi; A C Finarelli; M Panning; P Cordioli; C Fortuna; S Boros; F Magurano; G Silvi; P Angelini; M Dottori; M G Ciufolini; G C Majori; A Cassone Journal: Lancet Date: 2007-12-01 Impact factor: 79.321
Authors: Simona Ozden; Michel Huerre; Jean-Pierre Riviere; Lark L Coffey; Philippe V Afonso; Vincent Mouly; Jean de Monredon; Jean-Christophe Roger; Mohamed El Amrani; Jean-Luc Yvin; Marie-Christine Jaffar; Marie-Pascale Frenkiel; Marion Sourisseau; Olivier Schwartz; Gillian Butler-Browne; Philippe Desprès; Antoine Gessain; Pierre-Emmanuel Ceccaldi Journal: PLoS One Date: 2007-06-13 Impact factor: 3.240
Authors: Marion Sourisseau; Clémentine Schilte; Nicoletta Casartelli; Céline Trouillet; Florence Guivel-Benhassine; Dominika Rudnicka; Nathalie Sol-Foulon; Karin Le Roux; Marie-Christine Prevost; Hafida Fsihi; Marie-Pascale Frenkiel; Fabien Blanchet; Philippe V Afonso; Pierre-Emmanuel Ceccaldi; Simona Ozden; Antoine Gessain; Isabelle Schuffenecker; Bruno Verhasselt; Alessia Zamborlini; Ali Saïb; Felix A Rey; Fernando Arenzana-Seisdedos; Philippe Desprès; Alain Michault; Matthew L Albert; Olivier Schwartz Journal: PLoS Pathog Date: 2007-06 Impact factor: 6.823
Authors: Alissa R Young; Marissa C Locke; Lindsey E Cook; Bradley E Hiller; Rong Zhang; Matthew L Hedberg; Kristen J Monte; Deborah J Veis; Michael S Diamond; Deborah J Lenschow Journal: PLoS Pathog Date: 2019-08-29 Impact factor: 6.823