Springe zum Hauptteil

Institut für Medizinische Virologie und Epidemiologie der Viruskrankheiten

610

Adresse: Elfriede-Aulhorn-Str. 6
72076 Tübingen


Telefonnummer: 07071 29-80247


Faxnummer: 07071 29-5790


E-Mail-Adresse: sekretariat.​iftner@​med.​uni-​tuebingen.​de


Research Stubenrauch Lab

The HPV replication cycle

HPV infect and complete their replication cycle in keratinocyte cells that are the main constituents of mucosal and cutaneous epithelium. In basal epithelial cells low levels of HPV genome replication and expression of early viral gene products can be observed. Production of infectious HPV occurs only in the upper layers of the infected epithelium. 

  • We aim to understand the regulation of the different phases of the HPV replication cycle in order to identify key regulatory events that can be targeted by antivirals.

Contact

Head

frontend.sr-only_#{element.contextual_1.children.icon}: Prof. Dr. Frank Stubenrauch


frontend.sr-only_#{element.contextual_1.children.icon}: +49 7071 29-81553


E-Mail-Adresse: frank.stubenrauch@med.uni-tuebingen.de


The HPV genome is a double-stranded, covalently closed DNA molecule of 8kbp that is packaged in a chromatinized form. The viral E1 and E2 proteins are the key replication activators and form a complex that recognizes the viral origin. E1 acts as DNA helicase and recruits host cell proteins to initiate the replication of the genome. E2 is not only a loader for the E1 helicase but also modulates viral transcription and acts as segregation factor for the viral genomes upon cell division.

Our studies have uncovered that HPV encode E8^E2, an alternative E2 protein, which limits viral replication in undifferentiated cells by repressing viral transcription and E1/E2-dependent DNA replication. Using a panel of different technologies (immunoprecipitation-mass spectrometry, fluorescence microscopy, RNA interference, transcription and replication reporter assays), we have identified the cellular NCoR/SMRT repressor complex as a mediator of E8^E2´s repression activities.

  • we investigate the molecular mechanism of repression by the E8^E2-NCoR/SMRT complex
  • we investigate the long-term phenotypes of E8^E2 knock out PV genomes in tissue culture and animal models

we identify and characterize post-translational modifications (phosphorylation, acetylation, etc.) of the viral replication proteins E1, E2 and E8^E2C

HPV restriction factors

Viral infections can be detected by host cell sensors that initiate countermeasures to restrict viral replication. These countermeasures often involve the secretion of members of the interferon family that induce signal transduction cascades to activate hundreds of target genes (interferon stimulated genes, ISGs) which can interfere with virus replication. Interferon-kappa (IFNK) is unique among IFNs as it is constitutively expressed in human keratinocytes and thus is presumably responsible for the constitutive expression of antiviral restriction factors.

  • We aim to identify interferon-kappa regulated restriction factors for HPV

Selected Publications:

  • Identification and Functional Characterization of Phosphorylation Sites of the Human Papillomavirus 31 E8^E2 Protein. van de Poel S, Dreer M, Velic A, Macek B, Baskaran P, Iftner T, Stubenrauch F. J Virol. 2018 Jan 30;92(4).
  • Control of viral replication and transcription by the papillomavirus E8^E2 protein. Dreer M, van de Poel S, Stubenrauch F. Virus Res. 2017 Mar 2;231:96-102.
  • Interaction of NCOR/SMRT Repressor Complexes with Papillomavirus E8^E2C Proteins Inhibits Viral Replication. Dreer M, Fertey J, van de Poel S, Straub E, Madlung J, Macek B, Iftner T, Stubenrauch F. PLoS Pathog. 2016 Apr 11;12(4):e1005556.
  • Interferon Kappa Inhibits Human Papillomavirus 31 Transcription by Inducing Sp100 Proteins. Habiger C, Jäger G, Walter M, Iftner T, Stubenrauch F. J Virol. 2015 Oct 21;90(2):694-704.
  • The viral E8^E2C repressor limits productive replication of human papillomavirus 16. Straub E, Dreer M, Fertey J, Iftner T, Stubenrauch F. J Virol. 2014 Jan;88(2):937-47

Zertifikate und Verbände

Cookie Einstellungen
Bitte treffen Sie eine Auswahl um fortzufahren.
Weitere Informationen zu den Auswirkungen Ihrer Auswahl finden Sie unter Hilfe.
 
Um fortfahren zu können, müssen Sie eine Cookie-Auswahl treffen.

Cookies zulassen:
Wir setzen das Analysetool Google Analytics ein, um Besucher-Informationen wie z.B. Browser, Land, oder die Dauer, wie lange ein Benutzer auf unserer Seite verweilt, zu messen. Ihre IP-Adresse wird anonymisiert übertragen, die Verbindung zu Google ist verschlüsselt.

Nur notwendige Cookies zulassen:
Wir verzichten auf den Einsatz von Analysetools. Es werden jedoch technisch notwendige Cookies, die eine reibungslose Navigation und Nutzung der Webseite ermöglichen, gesetzt (beispielsweise den Zugang zum zugangsbeschränkten Bereich erlauben).

Sie können Ihre Cookie-Einstellung jederzeit auf der Seite Datenschutzerklärung ändern. Zum Impressum.

Zurück

Cookies zulassen Nur notwendige Cookies zulassen