Figure 5. Overview of the observations relating to the interplay between innate immune response and the viral genome in hepatitis C virus control.
(a) Infected individuals with IFNL4 CC genotype (37% of the HCV genotype 3a infected patients) show high rates of spontaneous and treatment-induced clearance of HCV. IFNL4 is not expressed, which in turn induces a weaker and possibly differential interferon-stimulated genes (ISG) expression. The host environment is associated with weaker purifying selection and allows viral mutations associated with a better replicative fitness to accumulate, leading to higher viral load. In this group of patients, 67% are infected by a virus with a serine at position 2414 and 33% with a different amino-acid. (b) Infected individuals with IFNL4 non-CC genotypes (63% of the HCV genotype 3a infected patients), have lower rates of spontaneous and treatment-induced clearance of HCV. IFNL4 is expressed and induces ISGs that collectively establish an antiviral state hostile to viral replication. This hostile environment induces a high selective pressure and fewer viral mutations can accumulate. Although the serine at position 2414 (compared to non serine) is associated with lower viral load, it is highly prevalent in this group of patients (85% are infected by a virus with a serine at position 2414 and 15% with a different amino-acid).