Current therapies control viral infection and reduce progressive liver disease. However, due to the unique HBV replication cycle viral elimination is virtually absent. Around 5 %of HBV infected patients are co-infected with hepatitis D virus (HDV) resulting to more rapid progression of liver disease. HBV/HDV co-infection remains very difficult to treat. Recently, the sodium taurocholate co-transporting polypeptide (NTCP) has been identified as a functional receptor of HBV and HDV. In this BGB324 in vitro study we aimed to establish a high-throughput HBV and HDV infection

model system to identify novel targets for viral cure. Methods: To develop high-thoughput models for viral infection, we generated a panel of hepatoma cell lines stably overexpressing hNTCP. HBV infectious particles were purified from the serum of virus- infected patients

and recombinant HDV and HBV infectious particles were produced in cell lines. Viral infections and their detection were optimized using various protocols including the use of automated systems. Results: Using viral protein-specific immunofluorescence, Northern Blot, HDV RNA-specific RT-PCR, HBV DNA-specific qPCR, we demonstrate that stable cell lines are highly susceptible to HDV and HBV infections. Screening a large series of cell culture conditions and Erlotinib ic50 experimental conditions, we established a protocol allowing robust detection of infections in a high-throughput format of 96 well plates. We validated the feasibility and robustness of the system by RNAi-mediated silencing of NTCP expression, antiviral peptides and Cyclosporin A showing easily detectable and quantifiable inhibition of infection. Targeted RNAi screens are underway to identify host-dependency factors for the complete viral life cycle. Conclusions: In conclusion, we have established high-throughput model systems for HDV and HBV infection. These systems will MCE公司 be useful for discovery of novel targets and antivirals

for viral cure. Disclosures: David Durantel – Grant/Research Support: Hoffman-La-Roche Ltd, Gilead Sciences, Novira Therapeutics Fabien Zoulim – Consulting: BMS, Gilead, Roche; Grant/Research Support: BMS, Gilead, Roche; Speaking and Teaching: BMS, Gilead The following people have nothing to disclose: Eloi R. VERRIER, Charlotte Bach, Laura Heydmann, Amelie Weiss, Rajeevkumar G. Tawar, Daniel Felmlee, Sarah Durand, Francois Habersetzer, Michel Doffoel, Catherine Schuster, Laurent Brino, Camille C. Sureau, Mirjam B. Zeisel, Thomas F. Baumert Background and aims: HBV/HDV co-infection is the most aggressive form of chronic viral hepatitis. HDV replication is not susceptible to currently available direct anti-HBV drugs, and sustained response to interferon alpha therapy occurs in less than a third of the patients, underlining the need for new therapies.