Showing papers by "Darius Moradpour published in 2006"

Molecular virology of hepatitis C virus (HCV): 2006 update.

Abstract: Fascinating progress in the understanding of the molecular biology of hepatitis C virus (HCV) was achieved recently. The replicon system revolutionized the investigation of HCV RNA replication and facilitated drug discovery. Novel systems for functional analyses of the HCV glycoproteins allowed the validation of HCV receptor candidates and the investigation of cell entry mechanisms. Most recently, recombinant infectious HCV could be produced in cell culture, rendering all steps of the viral life cycle, including entry and release of viral particles, amenable to systematic analysis. In this review, we summarize recent advances and discuss future research directions.

NMR structure and molecular dynamics of the in-plane membrane anchor of nonstructural protein 5A from bovine viral diarrhea virus.

Abstract: Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a monotopic membrane protein anchored to the membrane by an N-terminal in-plane amphipathic alpha-helix. This membrane anchor is essential for the assembly of a functional viral replication complex. Although amino acid sequences differ considerably, putative membrane anchors with amphipathic features were predicted in NS5A from related Flaviviridae family members, in particular bovine viral diarrhea virus (BVDV), the prototype representative of the genus Pestivirus. We report here the NMR structure of the membrane anchor 1-28 of NS5A from BVDV in the presence of different membrane mimetic media. This anchor includes a long amphipathic alpha-helix of 21 residues interacting in-plane with the membrane interface and including a putative flexible region. Molecular dynamic simulation at a water-dodecane interface used to mimic the surface separating a lipid bilayer and an aqueous medium demonstrated the stability of the helix orientation and the location at the hydrophobic-hydrophilic interface. The flexible region of the helix appears to be required to allow the most favorable interaction of hydrophobic and hydrophilic side chain residues with their respective environment at the membrane interface. Despite the lack of amino acid sequence similarity, this amphipathic helix shares common structural features with that of the HCV counterpart, including a stable, hydrophobic N-terminal segment separated from the more hydrophilic C-terminal segment by a local, flexible region. These structural conservations point toward conserved roles of the N-terminal in-plane membrane anchors of NS5A in replication complex formation of HCV, BVDV, and other related viruses.

Therapie der chronischen Hepatitis C

Abstract: Die Infektion mit dem Hepatitis-C-Virus (HCV) ist weltweit eine der haufigsten Ursachen der chronischen Hepatitis, Leberzirrhose und des hepatozellularen Karzinoms. In diesem Beitrag werden der aktuelle Stand und neue Entwicklungen auf dem Gebiet der Therapie der chronischen Hepatitis C kurz zusammengefasst. Die Standardtherapie mit pegyliertem Interferon-α und Ribavirin fuhrt bei bis zu 40–50% der Genotyp-1- und ca. 80% der Genotyp-2- und -3-infizierten Patienten zur anhaltenden Viruselimination. Eine besondere Bedeutung kommt der Erkennung und Beeinflussung von Kofaktoren der Krankheitsprogression zu (Alkohol- und Nikotinkarenz bzw. -reduktion, Impfung gegen Hepatitis A und B, Reduktion von Ubergewicht). Aufbauend auf einem verbesserten Verstandnis der molekularen Virologie und Pathogenese der Hepatitis C werden heute vielversprechende neue praventive und therapeutische Strategien exploriert.

Hépatologie : Gastro-entérologie

Abstract: Les traitements par interferon pegyle (PEG-IFN-α), lamivudine et adefovir ont considerablement ameliore les perspectives des patients avec une hepatite B chronique De nouveaux analogues nucleos(t)ides ont fait l'objet d'etudes positives et devraient permettre des traitements combines plus efficaces Dans l'hepatite auto-immune, en cas de non-reponse ou d'intolerance au traitement de prednisone et d'imurek, le mycophenolate mofetil peut etre envisage L'acide ursodesoxycholique a la dose de 13-15 mg/kg/j reste le traitement de premier choix de la cirrhose biliaire primitive Il doit etre administre le plus precocement possible pour ameliorer la survie des patients Dans le traitement des steatopathies non alcooliques, les thiazolidinediones apparaissent tres prometteuses mais doivent encore faire l'objet d'etudes complementaires