Expressions of inhibitory checkpoint molecules in acute and chronic HBV and HCV infections: Implications for therapeutic monitoring and personalized therapy

The function of T cells is tightly controlled by positive and negative regulations to ensure both successful pathogen elimination and limitation of immune-mediated pathology. One of the mechanisms to negatively regulate the magnitude and duration of effector T cells is the expression of inhibitory checkpoint molecules (ICs) on the surface membrane of T cells. During acute viral infections, expression of these molecules is upregulated to limit the effector functions following T-cell activation. The expression is subsequently downregulated following viral clearance. In contrast, these molecules are continuously expressed in virus-specific T cells found in persistently infected patients, including cases of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV). The continuously high expression of ICs is responsible for the dysfunctional states of HBV- and HCV-specific T cells in chronic phases, known as T-cell exhaustion. Hence, understanding the regulation of their expression is essential to give insight into pathogenesis as well as the development of effective immune-based antiviral therapies. This review discusses recent updated research on expression of ICs during acute and chronic phases of HBV and HCV infections as well as during the clinical course of antiviral therapy.