Meeting Summary A Summary of the 18th International Symposium on Hepatitis C Virus and Related Viruses STEPHEN J. POLYAK,* CHIHIRO MORISHIMA,* JOHN D. SCOTT, ‡ PABLO GASTAMINZA, § ANDREA COX,  EVALDO STANISLAU AFFONSO DE ARAÚJO, ¶ MARTIN R. HIGGS, # YUEH–MING LOO,** LUCY GOLDEN–MASON, ‡‡,§§ BRETT D. LINDENBACH,  THOMAS F. BAUMERT, ¶¶ GLENN RANDALL, ## and MICHAEL GALE Jr** *Departments of Laboratory Medicine, ‡ Medicine, and **Immunology, University of Washington, Seattle, Washington; § Departamento de Biología Celular y Molecular, Centro Nacional de Biotecnología-CSIC, Madrid, Spain;  Department of Medicine, The Johns Hopkins University, Baltimore, Maryland; ¶ Department of Infectious Diseases, University of São Paulo Hospital das Clínicas, São Paulo, Brazil; # INSERM Unité 955, Créteil, France; ‡‡ GI/Hepatology, University of Colorado Denver, Aurora, Colorado; §§ Integrated Department of Immunology, University of Colorado Denver and National Jewish Hospital, Denver, Colorado;  Section of Microbial Pathogenesis, Yale School of Medicine, New Haven, Connecticut; ¶¶ INSERM Unité 748, University of Strasbourg, Strasbourg, France; and ## Department of Microbiology, University of Chicago, Chicago, Illinois N early 800 researchers from around the world at- tended the 18th International Symposium on Hep- atitis C Virus and Related Viruses in Seattle, Washington, from September 8 to 12, 2011. The following report summarizes key aspects of the 96 oral presentations and 420 posters presented at the meeting. Viral Entry The entry session of this meeting focused on the molecular mechanism of the viral host cell entry pro- cesses, including the discovery of novel host factors in- volved in hepatitis C virus (HCV) entry. McKeating et al showed that HCV hijacks diffusing CD81–Claudin-1 coreceptors and relocalizes the complex to cholesterol-enriched domains for virus internalization. Catanese et al demonstrated that cell-cell transmission can occur in an SR-BI–independent manner. Using a functional RNA interference (RNAi) screen and pharma- cologic inhibitors, Zona et al uncovered the epidermal growth factor receptor signaling pathways relevant for viral entry in human hepatocytes. Sainz et al demon- strated a role for the Niemann-Pick–like 1 cholesterol absorption receptor (NPC1L1) in HCV entry. A potential role for SLAM family receptor CD229 in HCV attach- ment was presented by Cartier et al. Blaising et al dem- onstrated that entry inhibitors arbidol and silibinin in- terfere with early steps of viral trafficking. Finally, Haid et al showed evidence that Claudin family members may be used as entry factors in a genotype-dependent manner. Taken together, the findings presented highlight the rel- evance of host cell entry factors as targets for antivirals. Viral Replication New aspects of HCV replication were presented in the replication session. Qi et al presented a study on cre- ation and selection of viral genomes capable of replication and infection during interferon (IFN) treatment and sug- gested that insertions within core, p7, and NS5A were dif- ferentially selected by IFN treatment. Evans et al showed that RNA folding differences between the genotype 1b Con1 and genotype 2a JFH-1 genomes correlated with dif- ferences in replication efficiency, suggesting that cis-acting elements within NS5B may regulate translation. Denard et al described a new cell line that is highly permissive for HCV replicons but not to infection with JFH-1 virus particles. This cell line, HRP1, shows down-regulation of cyclic AMP- responsive element-binding protein 3-like protein 1 (CREB3L1). Manipulation of CREB3L1 expression sug- gested that CREB3L1 antagonizes the replication of HCV possibly via antiproliferative effects on cells. Tokunaga et al described a novel genotype 1a infectious culture system. Derived from a viral isolate (HCV-RMT) capable of infec- tion in the uPA-SCID mouse model, full-length adapted HCV-RMT genomes produced low levels of infectious virus, 150 focus-forming units per milliliter. Vaughan et al mapped interactions between RNA and the RNA-dependent RNA polymerase, indicating that NS5B residues 49 –56 and 66 –72 are in contact with the nascent RNA strand. Paul et al showed that the C-terminal region of NS4B plays an important role in homotypic interactions and formation of the membranous web. Finally, Camus et al showed that both core and NS5A interact with the cellular diacylglycerol acetyltransferase 1 (DGAT1) enzyme, which generates trig- lycerides that are loaded into lipid droplets (LDs). Knock- down and inhibitor experiments showed that DGAT1 is important for trafficking of both viral proteins to LDs. Thus, research on HCV replication is revealing new interac- tions between HCV proteins and viral RNA. Viral Assembly HCV assembly involves the HCV capsid protein known as core, several nonstructural proteins, and host cell components involved in lipoprotein assembly and secretion. Jones et al provided evidence of genetic cross- talk between core and NS3 proteins, where deficient in- fectious particle assembly of a core domain 1 mutant was efficiently rescued by a compensatory mutation within the helicase domain of NS3. Similarly, Konan et al showed that adaptation of assembly-deficient intergeno- © 2012 by the AGA Institute 0016-5085/$36.00 doi:10.1053/j.gastro.2011.11.002 GASTROENTEROLOGY 2012;142:e1– e5