Effects of different types of interferon on the expression of HCV replication-related microRNA

Abstract

To explore the effects of different types of interferon (IFN) on the expression of hepatitis C virus(HCV) replication-related miRNAs in human hepatocytes. The levels of miRNAs in Huh7 cells treated with types I (IFN-α, IFN-β), II (IFN-γ) and III (IFN-λ1) interferons (IFNs) were determined by real-time quantitative polymerase chain reaction (PCR). The levels of various miRNAs were compared among different IFN treatment groups. The expression of miRNA-196, miRNA-296, miRNA-351, miRNA-431 and miRNA-448 in IFN-α, IFN-β and IFN-λ1 treated groups was higher than that in control group (474.5 ± 57.7, 436.0 ± 37.8, 431.3 ± 43.5 vs 99.5 ± 2.4; 389.5 ± 44.0, 416.3 ± 36.7, 284.8 ± 20.9 vs 99.0 ± 0.8; 453.3 ± 51.1, 473.8 ± 24.0, 522.0 ± 40.3 vs 99.5 ± 2.1; 288.3 ± 44.9, 294.3 ± 29.9, 450.0 ± 29.5 vs 100.5 ± 2.4; 319.0 ± 35.4, 357.0 ± 27.5, 446.5 ± 61.2 vs 99.8 ± 1.0; all P < 0.05). The expression of miRNA-196, miRNA-351 and miRNA-448 in IFN-γ-treated group (271.3 ± 29.6, 140.5 ± 27.5, 177.8 ± 23.4) was higher than that in control group (all P < 0.05). But the expression of miRNA-431 and miRNA-296 had no significant difference between IFN-γ treated group and control group (both P > 0.05). The expression of miRNA-122 at difference concentrations (10, 100, 1 000 U/ml) of IFN-α, IFN-β, IFN-γ and IFN-λ1 (10, 100, 1 000 ng/ml) was lower than that in control group (49.3 ± 4.9, 32.0 ± 3.7, 24.5 ± 3.7 vs 99.5 ± 2.1; 53.5 ± 1.9, 35.5 ± 2.7, 25.8 ± 4.0 vs 98.8 ± 1.3; 60.8 ± 7.1, 43.8 ± 4.0, 33.5 ± 4.2 vs 99.3 ± 2.6; 50.0 ± 2.9, 35.5 ± 3.3, 22.3 ± 3.8 vs 100.3 ± 1.5; all P < 0.01). Different types of IFN increase the expression of miRNAs that inhibit HCV replication and decrease the expression of miRNA-122 that supports HCV replication. Thus the regulation of HCV replication-related miRNA expression is a general anti-HCV mechanism by different types of IFN. However, the regulation pattern by type II IFN is different from those by other types of IFNs, implying that type II IFN has different anti-HCV mechanisms from other types of IFN at miRNA level.