862 TRANSCRIPTIONAL-METABOLIC REPROGRAMMING OF HCV-INFECTION FROM PRIMARY HUMAN HEPATOCYTES CO-CULTURES TO CLINICAL SAMPLES

Abstract

observed. In the present study we have evaluated a novel strategy to prevent HCV infection using a lectin, Griffithsin (GRFT), that specifically binds N-linked high mannose oligosaccharides that are present on the viral envelope. The antiviral effect of GRFT was evaluated in vitro using the HCV pseudoparticles (HCVpp) and HCV cell culture (HCVcc) systems. We will demonstrate that pre-incubation of HCVpp and HCVcc with GRFT prevents infection of Huh-7 hepatoma cells. Furthermore, GRFT interferes with direct cell-to-cell transmission of HCV. GRFT acts at an early phase of the viral life cycle by interfering in a genotype-independent fashion with the interaction between the viral envelope proteins and the receptor CD81. The capacity of GRFT to prevent infection in vivo was evaluated using uPA-SCID mice that harbor human primary hepatocytes in their liver (chimeric mice). In this proof-of-concept trial we demonstrated that GRFT can mitigate HCV infection of chimeric mice. Treated animals that did become infected displayed a considerable delay in the kinetics of the viral infection. Our data demonstrate that GRFT can prevent HCV infection in vitro and mitigate HCV infection in vivo. GRFT treatment of chronically infected HCV patients undergoing liver transplantation may be a suitable strategy to prevent infection of the liver allograft.