Apoptosis-Related Gene Expression in an Adult Cohort with Crimean-Congo Hemorrhagic Fever

• Published in: PloS one Vol. 11; no. 6; p. e0157247
• Main Authors: Guler, Nil, Eroglu, Cafer, Yilmaz, Hava, Karadag, Adil, Alacam, Hasan, Sunbul, Mustafa, Fletcher, Tom E, Leblebicioglu, Hakan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-06-2016; Public Library of Science (PLoS)
• Subjects: Activation; Adult; Adults; Aged; Apoptosis; Apoptosis - genetics; Apoptosis Regulatory Proteins - genetics; Biology and Life Sciences; Bleeding; Blood; Cancer; Cell cycle; Cohort Studies; Correlation analysis; Crimean hemorrhagic fever; Cross-Sectional Studies; Evaluation; Fatalities; Female; Fever; Gene Expression; Genome, Viral - genetics; Hemorrhage; Hemorrhagic Fever Virus, Crimean-Congo - genetics; Hemorrhagic Fever Virus, Crimean-Congo - physiology; Hemorrhagic Fever, Crimean - genetics; Hemorrhagic Fever, Crimean - pathology; Hemorrhagic Fever, Crimean - virology; Host-Pathogen Interactions; Humans; Infections; Infectious diseases; Laboratories; Leukocytes; Leukopenia; Ligands; Longitudinal studies; Male; Medical prognosis; Medicine; Medicine and health sciences; Middle Aged; Mortality; Pathogenesis; Polymerase Chain Reaction; Proteins; Real time; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleic acid; RNA; Severity of Illness Index; Thrombocytopenia; Turkey; Viral infections; Viruses; Young Adult; Germany; Turkey
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0157247

Crimean-Congo Hemorrhagic Fever (CCHF) is a life threatening acute viral infection characterized by fever, bleeding, leukopenia and thrombocytopenia. It is a major emerging infectious diseases threat, but its pathogenesis remains poorly understood and few data exist for the role of apoptosis in acute infection. We aimed to assess apoptotic gene expression in leukocytes in a cross-sectional cohort study of adults with CCHF. Twenty participants with CCHF and 10 healthy controls were recruited at a tertiary CCHF unit in Turkey; at admission baseline blood tests were collected and total RNA was isolated. The RealTime ready Human Apoptosis Panel was used for real-time PCR, detecting differences in gene expression. Participants had CCHF severity grading scores (SGS) with low risk score (10 out of 20) and intermediate or high risk scores (10 out of 20) for mortality. Five of 20 participants had a fatal outcome. Gene expression analysis showed modulation of pro-apoptotic and anti-apoptotic genes that facilitate apoptosis in the CCHF patient group. Dominant extrinsic pathway activation, mostly related with TNF family members was observed. Severe and fatal cases suggest additional intrinsic pathway activation. The clinical significance of relative gene expression is not clear, and larger longitudinal studies with simultaneous measurement of host and viral factors are recommended.