A siege of hepatitis: immune boost for viral hepatitis

Abstract

Finding mechanisms of viral resistance and new ways to tackle chronic hepatitis will help find a cure for this disease. In ‘Bench to Bedside’, Christopher Walker and Benoît Callendret highlight studies showing that overcoming immune exhaustion during chronic infection by blocking several inhibitory pathways of T cells may restore an adequate immune response. In ‘Bedside to Bench’, Lawrence Corey, Joshua Schiffer and John Scott discuss recent advances in antiviral therapy with protease inhibitors and the findings of a mathematical model that predicts possible single and double mutations prior to antiviral therapy.

Figure 1

Multiple inhibitory pathways may be activated in the exhausted CD8⁺ T cells in the persistently infected liver, including PD-1 and TIM-3. Blockade of one inhibitory pathway may partially restore effector functions. Blocking antibodies may be directed against the PD-1 and TIM-3 receptors or possibly their ligands (PD-L1 and PD-L2 (PD-L1/L2) and galectin-9, respectively). Full rescue of CD8⁺ T cell exhaustion may require blockade of two or more inhibitory pathways, or a combination of pathway blockade, vaccination and/or virus suppression via direct-acting antivirals (DAA). Sustained restoration of CD4⁺ T cell function may be also crucial for a clinical cure, particularly in chronic hepatitis B. How CD4⁺ T cells are silenced, and the pathways to rescue this silencing, are still unknown.