Tätigkeitsbericht 2007/2008 8 200 / 7 0 20 Tätigkeitsbericht Stiftung bürgerlichen Rechts Martinistraße 52 · 20251 Hamburg Tel.: +49 (0) 40 480 51-0 · Fax: +49 (0) 40 480 51-103 [email protected] · www.hpi-hamburg.de Impressum Verantwortlich Prof. Dr. Thomas Dobner für den Inhalt Dr. Heinrich Hohenberg Redaktion Dr. Angela Homfeld Dr. Nicole Nolting Grafik & Layout AlsterWerk MedienService GmbH Hamburg Druck Hartung Druck + Medien GmbH Hamburg Titelbild Neu gestaltete Fassade des Seuchenlaborgebäudes Tätigkeitsbericht 2007/2008 Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg Martinistraße 52 · 20251 Hamburg Postfach 201652 · 20206 Hamburg Telefon: +49-40/4 80 51-0 Telefax: +49-40/4 80 51-103 E-Mail: [email protected] Internet: www.hpi-hamburg.de Das Heinrich-Pette-Institut ist Mitglied der Leibniz-Gemeinschaft (WGL) Internet: www.wgl.de Inhaltsverzeichnis Allgemeiner Überblick Vorwort ................................................................................................... 1 Die Struktur des Heinrich-Pette-Instituts .............................................. 2 Modernisierung des HPI erfolgreich abgeschlossen ............................ 4 60 Jahre HPI .............................................................................................. 5 Offen für den Dialog .............................................................................. 6 Preisverleihungen und Ehrungen .......................................................... 8 Personelle Veränderungen in den Jahren 2007 und 2008 ................... 10 Wissenschaftliche Highlights ................................................................. 12 Hohes Drittmittelaufkommen am HPI ................................................... 16 HPI fördert wissenschaftlichen Nachwuchs .......................................... 19 Gleichstellungsinitiative am HPI ............................................................ 22 Das „Leibniz Center for Infection“ (LCI) ................................................ 23 Programmbereich „Virus-Wirts-Wechselwirkungen“ Program Area “Virus-Host Interaction”* Introduction ............................................................................................. 27 Research Projects ..................................................................................... 29 ■ Helper function of wild-type p53 in Simian virus 40 induced cellular transformation ........................................................................... 29 ■ Role of c-Met in SV40-induced mammary tumorigenesis ....................... 30 ■ Mutant p53 gain of function in mammary carcinogenesis ...................... 32 ■ A preclinical model for monitoring treatment and prevention of metastasis in mammary carcinoma .................................................... 33 ■ Induction of a cellular immune response against SV40 induced mammary carcinoma in transgenic mice ................................... 34 ■ Steroid dependent control of HIV replication .......................................... 35 ■ Control of viral mRNA export by adenovirus regulatory proteins ............ 36 ■ Identification of a new substrate of the adenovirus/E1B-55K/E4orf6 ubiquitin ligase complex ......................................................................... 39 ■ Human adenovirus E4 region orf3/4 protein is required for efficient virus replication ................................................................... 40 ■ Localization and importance of the adenovirus E4orf4 protein during lytic infection .............................................................................. 41 ■ Intrinsic disorder in the amino terminus of human adenovirus type 5 E1B-55K and its related proteins ................................................. 42 ■ A novel 49K isoform of the adenovirus type 5 early region 1B 55K protein is sufficient to support viral replication ........................... 43 ■ Daxx-mediated negative regulation of adenovirus replication is counteracted by the adenovirus E1B-55K protein .............. 43 ■ Posttranscriptional processing of HIV-1 mRNA ........................................ 44 *Titel im Inhaltsverzeichnis sind z. T. gekürzt aufgelistet. ■ Combating drug resistance in HIV-1 infection ........................................ 47 ■ Eradication of HIV-1 proviral DNA from patient cells .............................. 49 ■ Rapid response kinetics to HLA-B57/58 Gag-restricted CTL epitopes is associated with slow disease progression in chronic HIV-1 infection .... 51 ■ Determinants of successful antiviral treatment of concomitant acute HCV/HIV coinfection ..................................................................... 53 ■ Crossing the Species Barrier: Role of Env-Receptor Interactions in Gammaretrovirus Infections ................................................................ 54 ■ Requirement of Activation for Hepatitis B Virus Infection ....................... 55 ■ Enzymatic treatment of duck hepatitis B virus: topology of the surface proteins for virions and noninfectious subviral particles .............. 55 ■ Entry of Duck Hepatitis B Virus into Primary Duck Liver and Kidney Cells .................................................................................... 55 ■ Elucidation of the SV40-induced DNA damage signaling cascades and their components utilized by SV40 .................................................. 56 ■ Role of the host’s p53 status in SV40 life cycle ....................................... 57 ■ Elucidation of the molecular mechanisms that underlie SV40-induced polyploidization ............................................................... 58 ■ Inhibition of duck hepatitis B virus infection of liver cells by combined treatment with viral e antigen and carbohydrates ............. 59 ■ Solution structure of stem-loop alpha of the hepatitis B virus post-transcriptional regulatory element .................................................. 60 ■ Analysis of Duck Hepatitis B Virus core protein phosphorylation and dephosphorylation ........................................................................... 61 ■ Transactivation activity of the X and PreS protein of duck hepatitis B virus are dispensible for DHBV infection in vitro and in vivo ................... 62 ■ Polyomavirus-encoded miRNAs .............................................................. 63 ■ A Global Analysis of Evolutionary Conservation Among Known and Predicted Gammaherpesvirus microRNAs ........................................ 65 ■ Monitoring the Epigenetic Fate of Gammaherpesvirus Genomes ............ 67 ■ A requirement for Drosha in the Maintenance of Kaposi's sarcoma-associated Herpesvirus Latency ................................................. 68 ■ A FACS-based FRET assay to analyze interactions between viral and cellular proteins in living cells .......................................................... 70 ■ Inhibition of Transferrin-Receptor Uptake by SIV and HIV Nef-alleles ...... 71 ■ Inefficient Nef-Mediated Downmodulation of CD3 and MHC-I Correlates with Loss of CD4+ T Cells in Natural SIV Infection ................. 72 ■ Single Nef Proteins from HIV-1 Subtypes C and F Fail to Up-Regulate Invariant Chain Cell Surface Expression .......................... 73 ■ Human Immunodeficiency Virus Type 1 Nef Expression Prevents AP-2-Mediated Internalization of the Major Histocompatibility Complex Class II-Associated Invariant Chain .............. 73 ■ Siglec expression on chimpanzee T-cells might contribute to the asymptomatic course of lentiviral infection in human primates ........ 75 ■ HIV-1 budding and persistence in macrophages ..................................... 75 ■ A serine phosphorylation site in HIV-1 Vpu is required for efficient counteraction of tetherin and replication in macrophages ... 77 ■ Viral determinants for AIDS-progression in pediatric HIV-1 subtype B and C infections .................................................................. 78 ■ Replication of ICP0-Null Mutant Herpes Simplex Virus Type 1 Is Restricted by both PML and Sp100 ..................................................... 78 ■ Duck Hepatitis B Virus Requires Cholesterol for Endosomal Escape during Virus Entry ............................................... 79 ■ Strong and selective inhibitors of hepatitis B virus replication among novel N4-hydroxy- and 5-methyl-beta-L-deoxycytidine analogues ........... 80 ■ Assembly and budding of a hepatitis B virus is mediated by a novel type of intracellular vesicles ........................................................ 81 ■ Avian Hepatitis B Viruses: Molecular and Cellular Biology, Phylogenesis and Host Tropism .............................................................. 82 ■ Efficiency of DHBV infection is restricted by an abortive entry pathway .. 83 ■ Secretion of duck hepatitis B virus occurs via exocytosis ......................... 83 ■ Naturally occurring adefovir resistance mutation rtI233V selected under adefovir therapy ............................................................. 85 ■ Cellular Determinants of HBV Replication ............................................... 85 ■ High resolution electron microscopical (EM)-analysis of the distribution of TNF receptor 1 ................................................................................... 86 ■ Cryotomography Ultrastructural analysis of cytomegalovirus tegument protein interactions ................................................................ 87 ■ Dynamic processes in organic and biological