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World J Hepatol. Oct 27, 2020; 12(10): 754-765
Published online Oct 27, 2020. doi: 10.4254/wjh.v12.i10.754
Tumor necrosis family receptor superfamily member 9/tumor necrosis factor receptor-associated factor 1 pathway on hepatitis C viral persistence and natural history
Julia Peña-Asensio, Eduardo Sanz-de-Villalobos, Joaquín Miquel, Juan Ramón Larrubia
Julia Peña-Asensio, Department of Systems Biology, Guadalajara University Hospital. University of Alcalá, Guadalajara E-19002, Guadalajara, Spain
Eduardo Sanz-de-Villalobos, Joaquín Miquel, Juan Ramón Larrubia, Translational Hepatology Unit, Guadalajara University Hospital, University of Alcalá, Guadalajara E-19002, Guadalajara, Spain
Author contributions: Peña-Asensio J and Larrubia JR wrote the manuscript; Sanz-de-Villalobos E and Míquel J revised the manuscript for important intellectual content; Larrubia JR designed the manuscript and revised the final version.
Supported by Instituto de Salud Carlos III and European Structural Funds in Spain; European Regional Development Fund, No. PI19/00206.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Juan Ramón Larrubia, MD, MSc, PhD, Senior Lecturer, Staff Physician, Translational Hepatology Unit, Guadalajara University Hospital, University of Alcalá, Donante de Sangre St, Guadalajara E-19002, Guadalajara, Spain. juan.larrubia@uah.es
Received: June 13, 2020
Peer-review started: June 13, 2020
First decision: July 30, 2020
Revised: August 1, 2020
Accepted: September 25, 2020
Article in press: September 25, 2020
Published online: October 27, 2020
Core Tip

Core Tip: Tumor necrosis factor receptor-associated factor 1 (TRAF1) is the signal transducer of the positive checkpoint tumor necrosis family receptor superfamily member 9 (4-1BB), essential in the activation of adaptive immune response. During persistent hepatitis C virus (HCV) infection, this transducer is down-regulated via transforming growth factor beta 1, linked to T cell exhaustion. Interleukin-7 can restore TRAF1 expression and improve T cell reactivity but only in patients with mild evolution, while cases with a more aggressive progression also need the modulation of other negative co-stimulatory molecules. Therefore, TRAF1 dynamics defines a new pathogenic model that explains the different level of T cell exhaustion and progression during HCV infection and supports the rationale for immunotherapeutic strategies in chronic viral infections.