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Abstract
The 16th International Symposium on Hepatitis C Virus and Related Viruses took place in Nice, France, on October 3–7, 2009, almost exactly 20 years after Michael Houghton and colleagues reported discovery of the hepatitis C virus (HCV).1 At that time, the disease was known as “non-A, non-B hepatitis,” and its prevalence was underestimated. Now, approximately 170 million individuals worldwide are infected; chronic HCV infection is the leading indication for liver transplantation and one of the principal causes of primary liver cancer in industrialized countries. The inaugural lecture, given by David Thomas, gave faces to this disease, showing interviews with HCV-infected patients who reported their sufferings, achievements, and hopes. The symposium was endorsed by the European Association for the Study of the Liver (EASL) and the French National Agency for AIDS and Viral Hepatitis Research (ANRS). Nine keynote lectures were given by world-recognized experts, and there were 97 oral presentations and 340 posters presented. A brief summary of the highlights of the meeting is presented here. A complete listing of authors and institutions for each study included in this summary (Supplementary Material) can be accessed online at www.gastrojournal.org.
Viral Entry
The early steps of the HCV life cycle were introduced before the official opening of the meeting by a short didactic video developed by the iCAP facilities at the University of Lyon 1 (Figure 1). The video can be viewed and downloaded at http://www.ibcp.fr/video/ download_hcv.php?format_mov. Viral entry was discussed by Jean Dubuisson in a keynote lecture as well as in 2 oral sessions and a poster session. A major breakthrough at the meeting was the presentation by Krey et al of a model of HCV E2 glycoprotein tertiary organization. Disulfide connectivity (also recently described by other groups), functional data, and secondary structure predictions allowed these investigators to thread the E2 polypeptide chain onto a class II fusion protein template. The model revealed the distribution of E2 amino acids among 3 different domains (DI, DII, DIII), mapped the CD81 binding site to the DI/DIII interface, and highlighted a strictly conserved segment of the polypeptide chain as a strong candidate for the fusion loop. This model will provide an invaluable structural framework to better understand the function of HCV envelope glycoproteins in the early steps of the HCV life cycle. Important progress has also been made in the understanding of the role of E2 envelope glycoprotein hypervariable region 1 (HVR1) (Bankwitz et al, Brice et al, McCaffrey et al, and Prentoe et al). This region does not appear to be required for RNA replication, assembly, or release in the HCVcc infectious virion system. However, HVR1 deletion strongly reduced the specific infectivity of low-density particles. Additionally, removal of HVR1 increased exposure of the CD81 binding site and sensitivity to neutralizing antibodies, previously shown in the HCV pseudoparticle model (HCVpp). These multiple functions suggest that HVR1 modulates HCV entry and the humoral immune response. Other important studies described the identification of a thiol isomerization-like motif in E1 sequence (Dean et al), the role of glycans in protecting neutralizing epitopes (Helle et al), the role of nonconserved domains of E1 and E2 from different genotypes in HCV entry (Albecka et al,
Viral Entry
The early steps of the HCV life cycle were introduced before the official opening of the meeting by a short didactic video developed by the iCAP facilities at the University of Lyon 1 (Figure 1). The video can be viewed and downloaded at http://www.ibcp.fr/video/ download_hcv.php?format_mov. Viral entry was discussed by Jean Dubuisson in a keynote lecture as well as in 2 oral sessions and a poster session. A major breakthrough at the meeting was the presentation by Krey et al of a model of HCV E2 glycoprotein tertiary organization. Disulfide connectivity (also recently described by other groups), functional data, and secondary structure predictions allowed these investigators to thread the E2 polypeptide chain onto a class II fusion protein template. The model revealed the distribution of E2 amino acids among 3 different domains (DI, DII, DIII), mapped the CD81 binding site to the DI/DIII interface, and highlighted a strictly conserved segment of the polypeptide chain as a strong candidate for the fusion loop. This model will provide an invaluable structural framework to better understand the function of HCV envelope glycoproteins in the early steps of the HCV life cycle. Important progress has also been made in the understanding of the role of E2 envelope glycoprotein hypervariable region 1 (HVR1) (Bankwitz et al, Brice et al, McCaffrey et al, and Prentoe et al). This region does not appear to be required for RNA replication, assembly, or release in the HCVcc infectious virion system. However, HVR1 deletion strongly reduced the specific infectivity of low-density particles. Additionally, removal of HVR1 increased exposure of the CD81 binding site and sensitivity to neutralizing antibodies, previously shown in the HCV pseudoparticle model (HCVpp). These multiple functions suggest that HVR1 modulates HCV entry and the humoral immune response. Other important studies described the identification of a thiol isomerization-like motif in E1 sequence (Dean et al), the role of glycans in protecting neutralizing epitopes (Helle et al), the role of nonconserved domains of E1 and E2 from different genotypes in HCV entry (Albecka et al,
Originalsprache | Englisch |
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Zeitschrift | Gastroenterology |
Jahrgang | 138 |
Ausgabenummer | 1 |
ISSN | 0016-5085 |
DOIs | |
Publikationsstatus | Veröffentlicht - 01.01.2010 |
Strategische Forschungsbereiche und Zentren
- Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)
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Bindung eines zellulären Chaperons an Proteasen verschiedener Viren - Interaktionsdeterminanten und Bedeutung für die virale Replikation
01.01.05 → 31.12.12
Projekt: DFG-Projekte › DFG Einzelförderungen