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. 2016 Jun 9;17(5):265–275. doi: 10.1038/gene.2016.24

Figure 5.

Figure 5

IFN-λ3 and IFN-λ4 expression, and spontaneous and IFN-based therapy-induced clearance of HCV infections in humans. The schematic is a summary and interpretation of data available so far from different studies (reviewed in ref. 15) dealing with HCV infections. All patients who get infected by HCV can be divided in to the three groups shown in the schematic. (a) Patients who spontaneously clear HCV are known to have higher levels of IFN-λ3 protein in their serum compared with patients who carry on with the infection108 and it is likely that their IFN-stimulated gene (ISG) levels are also influenced by the IFN-λ3 levels, thus helping to clear the virus infection. Once patients get chronically infected with HCV, they undergo IFN-α-ribavirin treatment for 24–48 weeks. (b, c) Those who do not respond to this therapy have high frequency of the functional IFN-λ4-generating allele ΔG at rs368234815 (ref. 14) and therefore are expected to express IFN-λ4.94 A recent study has documented that type III IFNs including IFN-λ2/3 and IFN-λ4 expression levels correlate with ISG expression in the liver of patients undergoing anti-HCV therapy.94 The IFN-λ2/3 and IFN-λ4 levels and their associated ISG levels are higher in the liver of patients who will eventually not respond to the therapy94 compared with those who will respond, suggesting that an unknown effect inhibits the expression of IFN-λ3 in the latter group of patients (shown as an ellipse in c). It seems that IFN-α-ribavirin treatment induces the expression of IFN-λ3 once treatment begins (depicted as a circle in c) preferably in those patients who will eventually respond to the treatment94 (These patients have lower frequency of the functional IFN-λ4-generating alleles14 and hence are shown without IFN-λ4 expression (c)). This induction is further dependent on whether the patients carry beneficial alleles at rs12979860. The patients who have the beneficial alleles show higher increase in their hepatic IFN-λ3 levels than those who do not, once treatment is initiated.94 A previous report also had seen similar changes in serum IFN-λ3 levels.109 The ISG levels are shown in correlation with IFN-λ3 expression.