1%) cDNA-uPA/SCID mice became positive for HCV RNA 8 weeks after HCV inoculation. Despite similar frequencies of HCV viremia, serum HCV RNA titers 2 weeks after infection in cDNA-uPA/SCID buy Ivacaftor were significantly higher than in uPA/SCID mice (6.6 ± 0.4 vs 8.1 ± 0.6 copy/mL, p<0.001). Conclusion: Humanized cDNA-uPA/SCID mice thus provide a more robust animal model useful for the study of hepatitis virus virology and development of antiviral drugs. Disclosures: Kazuaki Chayama - Consulting:

Abbvie; Grant/Research Support: Dainippon Sumitomo, Chugai, Mitsubishi Tanabe, DAIICHI SANKYO, Toray, BMS, MSD; Speaking and Teaching: Chugai, Mitsubishi Tanabe, DAIICHI SANKYO, KYO-RIN, Nihon Medi-Physics, BMS, Dainippon Sumitomo, MSD, ASKA, Astellas, AstraZeneca, Eisai, Olympus, GlaxoSmithKline, ZERIA, Bayer, Minophagen, JANSSEN, JIMRO, TSUMURA, Otsuka, Taiho, Nippon Kayaku, Nippon Shin- yaku, Takeda, AJINOMOTO, Meiji Seika, Toray The following people have nothing to disclose: Takuro Uchida, Nobuhiko Hiraga, Michio Imamura, Masataka Tsuge, Hiromi Abe, C. Nelson Hayes, Hiro-shi Aikata, Yuji Ishida, Chise Tateno, Katsutoshi Yoshizato, Kazunari Murakami Aim: Immunodeficient mice transplanted with human hepato-cytes Deforolimus in vitro are available for the study of human hepatitis

viruses. Recently, human hepatocytes were also successfully transplanted in herpes simplex virus type-1 thymidine kinase (TK)-NOG mice. In this study, we attempted to infect hepatitis viruses in humanized TK-NOG mice and urokinase-type plas-minogen activator-severe combined immunodeficiency (uPA-SCID) mice. Methods: Eight-week-old TK-NOG mice were injected intraperitoneally with

6 mg/kg of ganciclovir (GCV) twice a day. Two days after the first MCE公司 injection, mice were re-injected with the same amount of GCV. Seven days after the first GCV injection, mice were transplanted with 1 × 106 of human hepatocytes. Eight weeks after hepatocyte transplantation, TK-NOG and uPA/SCID mice with HSA levels over 1.0 mg/mL were injected intravenously with 50 of either hepatitis B virus (HBV)- or hepatitis C virus (HCV)-positive human serum samples. Mice serum samples were obtained every two weeks after virus infection, and HBV DNA or HCV RNA levels were measured by real-time PCR. The concentration of human serum albumin (HSA), which is correlated with the human hepatocyte repopulation index (RI), was measured by ELISA. Results: In TK-NOG mice (n=194), serum alanine aminotransferase (ALT) levels one week after GCV administration and HSA levels 8 weeks after hepatocyte transplantation showed a positive correlation, indicating that the higher the serum ALT level, the higher the RI. All humanized TK-NOG (n=43) and uPA/SCID mice (n=36) injected with HBV infected serum developed vire-mia irrespective of lower replacement index. Incidence of HCV viremia was also high in TK-NOG mice regardless of the RI. In contrast, the frequency of HCV viremia was much lower in uPA-SCID mice having low RI.