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

Figure 5 Tumor necrosis factor receptor-associated factor 1-related pathogenic mechanism involved in T cell exhaustion and liver fibrosis progression during persistent hepatitis C virus infection. Scheme showing transforming growth factor beta 1-mediated CD8 T cell impairment during chronic hepatitis C virus infection due to tumor necrosis factor receptor-associated factor 1 (TRAF1). In patients with mild clinical progression, T cell reactivity can be restored by TRAF1 upregulation with interleukin (IL)-7 treatment. Those with rapid fibrosis or with long-term infection need IL-7 treatment combined with programmed cell death protein 1 blockade. Cases with rapid fibrosis and long infection duration cannot be restored, probably due to T cell deletion. Ag: Antigen; 4-1BB: Tumor necrosis family receptor superfamily member 9; 4-1BBL: 4-1BB-ligand; PD-1: Programmed cell death protein-1; HCV: Hepatitis C virus; TRAF1: Tumor necrosis factor receptor-associated factor 1; TGF: Transforming growth factor; IL: Interleukin; APC: Antigen-presenting cell; TCR: T cell receptor.