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Chronic hepatitis C virus infection triggers spontaneous differential expression of biosignatures associated with T cell exhaustion and apoptosis signaling in peripheral blood mononucleocytes
University of Malaya, Malaysia.
University of Malaya, Malaysia.
University of Malaya, Malaysia.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
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2015 (English)In: Apoptosis (London), ISSN 1360-8185, E-ISSN 1573-675X, Vol. 20, no 4, 466-480 p.Article in journal (Refereed) Published
Abstract [en]

Persistent hepatitis C virus (HCV) infection appears to trigger the onset of immune exhaustion to potentially assist viral persistence in the host, eventually leading to hepatocellular carcinoma. The role of HCV on the spontaneous expression of markers suggestive of immune exhaustion and spontaneous apoptosis in immune cells of chronic HCV (CHC) disease largely remain elusive. We investigated the peripheral blood mononuclear cells of CHC patients to determine the spontaneous recruitment of cellular reactive oxygen species (cROS), immunoregulatory and exhaustion markers relative to healthy controls. Using a commercial QuantiGenePlex(A (R)) 2.0 assay, we determined the spontaneous expression profile of 80 different pro- and anti-apoptotic genes in persistent HCV disease. Onset of spontaneous apoptosis significantly correlated with the up-regulation of cROS, indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2/prostaglandin H synthase (COX-2/PGHS), Foxp3, Dtx1, Blimp1, Lag3 and Cd160. Besides, spontaneous differential surface protein expression suggestive of T cell inhibition viz., TRAIL, TIM-3, PD-1 and BTLA on CD4+ and CD8+ T cells, and CTLA-4 on CD4+ T cells was also evident. Increased up-regulation of Tnf, Tp73, Casp14, Tnfrsf11b, Bik and Birc8 was observed, whereas FasLG, Fas, Ripk2, Casp3, Dapk1, Tnfrsf21, and Cflar were moderately up-regulated in HCV-infected subjects. Our observation suggests the spontaneous onset of apoptosis signaling and T cell exhaustion in chronic HCV disease.

Place, publisher, year, edition, pages
Springer Verlag (Germany) , 2015. Vol. 20, no 4, 466-480 p.
Keyword [en]
Apoptosis; Caspase; Hepatitis C; Spontaneous immune exhaustion; TRAIL
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-116813DOI: 10.1007/s10495-014-1084-yISI: 000350669500005PubMedID: 25577277OAI: diva2:800768

Funding Agencies|High Impact Research, University of Malaya [UM.C.625/1/HIR/139]; HIRG-MOHE Grant of University of Malaya [A000003-50001]; Swedish Research Council [AI52731]; Swedish Physicians against AIDS Research Foundation; Swedish International Development Cooperation Agency; SIDA SARC; VINNMER for Vinnova; Linkoping University Hospital Research Fund; CALF; Swedish Society of Medicine; University of Malaya Research Grant (UMRG) of the Health and Translational Medicine Research Cluster, University of Malaya [RG448-12HTM]

Available from: 2015-04-07 Created: 2015-04-07 Last updated: 2015-04-07

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Ellegård, RadaLarsson, Marie
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