Tumor necrosis family receptor superfamily member 9/tumor necrosis factor receptor-associated factor 1 pathway on hepatitis C viral persistence and natural history

Hepatitis C virus (HCV) infection is an excellent immunological model for understanding the mechanisms developed by non-cytopathic viruses and tumors to evade the adaptative immune response. The antigen-specific cytotoxic T cell response is essential for keeping HCV under control, but during persist...

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Published in:World journal of hepatology 2020-10, Vol.12 (10), p.754-765
Main Authors: Peña-Asensio, Julia, Sanz-de-Villalobos, Eduardo, Miquel, Joaquín, Larrubia, Juan Ramón
Format: Article
Language:English
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Summary:Hepatitis C virus (HCV) infection is an excellent immunological model for understanding the mechanisms developed by non-cytopathic viruses and tumors to evade the adaptative immune response. The antigen-specific cytotoxic T cell response is essential for keeping HCV under control, but during persistent infection, these cells become exhausted or even deleted. The exhaustion process is progressive and depends on the infection duration and level of antigenemia. During high antigenic load and long duration of infection, T cells become extremely exhausted and ultimately disappear due to apoptosis. The development of exhaustion involves the impairment of positive co-stimulation induced by regulatory cytokines, such as transforming growth factor beta 1. This cytokine downregulates tumor necrosis factor receptor (TNFR)-associated factor 1 (TRAF1), the signal transducer of the T cell co-stimulatory molecule TNFR superfamily member 9 (known as 4-1BB). This impairment correlates with the low reactivity of T cells and an exhaustion phenotype. Treatment with interleukin-7 restores TRAF1 expression and rescues T cell effector function. The process of TRAF1 loss and its recovery is hierarchical, and more affected by severe disease progression. In conclusion, TRAF1 dynamics on T cells define a new pathogenic model that describes some aspects of the natural history of HCV, and sheds light on novel immunotherapy strategies for chronic viral infections and cancer.
ISSN:1948-5182
1948-5182
DOI:10.4254/wjh.v12.i10.754