Su1022 The Association of the CXCL10, Dpp-4 Gene Polymorphisms and Complementary Role for Unfavorable IL-28B Genotype in Prediction of Treatment Response in Asian Patients With Chronic Hepatitis C Virus Infection

Abstract

subcloned into pSilencer 4.1-CMV puro vectors, and confirmed by sequencing. Huh7.5 cells were transfected with each plasmid before or after exposure to Japanese Fulminant Hepatitis Virus-1 (JFH-1), an HCV genotype 2a strain, capable of infecting human liver cells. Media were sampled at several time points, and HCV RNA was quantified by real time RT-qPCR. HCV RNA levels were statistically normalized to HCV RNA levels in the media used to infect cells. RESULTS: At 72 h, JFH-1 HCV RNA levels in media from Huh7.5 cells in the control (no plasmid transfection) and those transfected by HB (negative control) were similar. JFH-1 HCV RNA levels in those transfected by analogs, X-94, X-12, 5B-74 and 5B46 before exposure to JFH-1 HCV were 6.5%, 1.8%, 5.8%, and 6.1%, respectively of the HB controls (Fig. 1), (p<0.001). JFH-1 RNA levels in media from Huh7.5 cells transfected with analogs, X-94, X-12, 5B-74 and 5B-46 after exposure to JFH-1 HCV were 1.8%, 1.8%, 2.7%, and 3.7%, respectively of the HB controls (Fig. 2), (p <0.001). Furthermore, the X12 analog whose secondary structure is identical, but sequence is only 12% identical to JFH-1 was also highly effective suggesting that secondary structure rather than antisense effects are involved. CONCLUSIONS: Transfection of liver cells with HCV structural analogs before or after exposure to infectious virus can inhibit HCV replication and secretion of virus by more than 90%. Stable expression of these analogs might provide protection against HCV infection and treatment of HCV infection resulting in a survival advantage.