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1008A AASLD ABSTRACTS HEPATOLOGY, October, 2015 using Chi-square test and logistic regression analysis. Results: In the CHB group, 28.5% were inactive carriers, 67.7% were HBe-antigen negative, 17.2% had cirrhosis, 6.5% had hepatocellular carcinoma and 4.4% were liver transplanted. 85.6% had already received treatment for CHB. The mean age and sex distribution differed significantly between the CHB and the SC groups (45.38±15.4 vs. 61.35±14.5; p
HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1009A HBV-specific CD8+ T cells was almost completely diminished in the absence of MHC class I expression on non-hematopoietic cells, resulting in more than 2,000 fold decrease in the number of HBV-specific CD8 T cells compared with their counterparts in MHC class I positive control animals. HBV-specific CD8+ T cells did not express granzyme B, either, even though they clearly recognized antigen and expressed activation marker CD69. Conclusion: These results suggest that cross-presentation by hematopoietic cells is required for the optimum expansion of HBV-specific CD8 T cells, but endogenous antigen presentation by non-hematopoietic cells, presumably hepatocytes, is far more essential in the expansion and cytolytic differentiation of HBV-specific CD8+ T cells. Disclosures: Yasuhito Tanaka - Grant/Research Support: Chugai Pharmaceutical CO., LTD., MSD, Bristol-Myers Squibb; Speaking and Teaching: janssen pharma, Bristol-Myers Squibb The following authors have nothing to disclose: Masanori Isogawa, Yasuhiro Murata, Keigo Kawashima 1641 Initial sites of hepadnavirus-host genome integration after de novo infection of HepaRG cells and woodchuck livers Ranjit Chauhan, Norma D. Churchill, Thomas I. Michalak; Molecular Virology and Hepatology Research Group, Memorial University, St. John’s, NF, Canada Backgound: HBV is highly oncogenic virus and its integration into human genome precedes development of hepatocellular carcinoma (HCC). It is expected that the sites and the spread of HBV integrations across human genome might be relevant to the establishment and progression of HCC. The initial sites of HBV-host DNA junctions remain unknown. Aim: To identify the earliest sites of hepadnavirus integration into host’s genome by exploring de novo infection of human hepatocyte-like HepaRG cells with authentic HBV and woodchucks infected with woodchuck hepatitis virus (WHV). Methods: HepaRG cells infected with HBV were investigated in 15 min, 30 min, 1 h, 3 h, 24 h, 72 h, 7 days (d), 10 d, 2 weeks (wk), 4 wk and 7 wk post-infection. Liver biopsies were obtained from woodchucks infected with WHV at 1 h or 3 h and at 6 wk post-infection (JVI 2008;82:8579). HepaRG cells were analyzed for HBV X gene integrations, while liver biopsies for WHV X and preS sequence integrations applying inverse-PCR followed by amplicon cloning and sequencing. Results: Intracellular HBV DNA and its replication intermediates became detectable in HepaRG cells from 1 h and remained present up to 7 wk post-exposure. HBV DNA integrations became identifiable in 1 h post-infection. Junctions of HBV X gene in retrotransposon sequences, such as LINE1 (long-interspersed nuclear element 1) and LINE2, became prominent from 3 days post-infection and they represented approximately half the virus-host junctions detected at that time. Insertions of HBV X integrant into other genes, including human satellite HSAT-II sequence, neurotrimin on chromosome (Ch) 11q25, ZNF-782 on Ch-9q22.3, myosin 3B on Ch-2q31.1, and ten-eleven translocation-1 gene (TET-1) on Ch-10q21.3 were also detected. In woodchucks, integration of WHV preS genomic sequence into MAML2 gene on Ch-11q21 (based on 88% homology with human) was identified in 1 h post-infection and WHV X gene integrants into unidentified so far woodchuck genes were evident in 1 h and 3 h post-infection. The HBV core promoter/enhancer-II region followed by enhancer I region and its WHV equivalent were predisposed to form the earliest junctions with host DNA. In addition, multiple virus-virus DNA joints were identified from 1 h post-infection onward in both HBV-infected cells and WHV-infected woodchuck livers. Conclusions: HBV DNA integrates very early into the host’s genome and may utilize retrotransposon elements and translocation genes from the early stages of infection for spread and induction of pro-oncogenic perturbations throughout the host’s genome. The predisposition to very early integration was also evident in natural WHV infection in woodchucks. Disclosures: The following authors have nothing to disclose: Ranjit Chauhan, Norma D. Churchill, Thomas I. Michalak 1642 An impact of cellular core-fucosylation in hepatitis B virus infection into hepatoma cell lines Eiji Miyoshi 2 , Shinji Takamatsu 1 , Mayuka Shimomura 1 , Yoshihiro Kamada 1,3 , Haruka Maeda 1 , Tomoaki Subajima 2 , Hayato Hikita 3 , Iijima Mayumi 4 , Yuta Okamato 5 , Ryo Misaki 5 , Kazuhito Fujiyama 5 , Tetsuo Takehara 3 , Keiji Ueda 6 , Shunichi Kuroda 4 ; 1 Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Japan; 2 Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduated School of Medicine, Suita, Japan; 3 Department of Gastroenterology and Hepatology, Osaka University Graduated School of Medicine, Suita, Japan; 4 Department of Bioengineering Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan; 5 Applied Microbiology Laboratory, International Center for Biotechnology, Osaka University, Suita, Japan; 6 Department of Microbiology, Osaka University Graduated School of Medicine, Suita, Japan Background & Aims: It is a well known fact that oligosaccharides on cell surface proteins such as growth factor receptors as well as virus/bacteria entry receptors regulate their functions dynamically. These oligosaccharide structures are regulated by a set of expression of several kinds of glycosyltransferase. In the present study, we investigated the involvement of glycosylation in hepatitis B virus (HBV) entry onto hepatoma cells. Methods: We used several kinds of hepatoma cell lines such as Huh7, Hep3B, Huh6 and HB611 cells. HB611 cells are established by transfection of tandem repeats of HBV genome DNA into Huh6 cells and secrete HBV-related antigens into the conditioned medium. Bio nanocapsules (BNC) are hollow particles consisting of HBV surface antigen (HBs) large proteins embedded in a unilamellar liposome, and used as pseudo-HBV virus. Incorporation of BNC in oligosaccharide remodeling hepatoma cells was evaluated by flow cytometer and con-focal microscopy. Oligosaccharide structure was analyzed with lectin blot, lectin microarray and mass spectrometry. To identify association molecules with sodium taurocholate cotransporting polypeptide (NTCP), which is one of major candidate for HBV receptors, immune-precipitation with NTCP antibody followed by LC-MS analyses was performed. Results: Transfection of glycosyltransferase genes into several kinds of hepatoma cells changed the level of BNC uptake. Among them, HB611 cells showed dramatic increases in BNC incorporation, compared to parental cell, Huh6 cells. As a result from glycomic analyses, increases in cellular fucosylation and sialylation were observed in HB611 cells. Knock down of fucosyltransferase 8 (FUT8) gene as well as sialidase treatment decreased BNC entry into HB611 cells. In contrast, overexpression of FUT8 in Huh6 cells increased BNC incorporation. Addition of core-fucose specific lectin, Pholiota squarrosa lectin (PhoSL) in the conditioned medium inhibited the entry of BNC into HB611 cells. While expression of sodium taurocholate cotransporting polypeptide (NTCP) was lower in HB611 cells than Huh6 cells, levels of co-precipitated molecules with NTCP were dependent on levels of core fucosylation, suggesting that core-fucosylation regu-
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1312A AUTHOR INDEX HEPATOLOGY, Octo
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1366A CATEGORY INDEX HEPATOLOGY, Oc
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