Experimentelle Virologie

Forschungsschwerpunkte

  • Persistierende virale Infektionen
  • Angeborene Immunität gegen Retroviren
  • Grundlagen zellulärer und molekularer Immunabwehrmechanismen
  • Immunregulation bei Retrovirus Infektionen
  • Immuntherapie gegen retrovirale Infektionen und Virus-induzierte Tumoren
  • Entwicklung von Impfstoffen gegen Retroviren
  • Antivirale Aktivität von Interferonen

 

Retrovirale Infektionen

Trotz weltweit intensiver Forschung ist es bisher nicht gelungen, Impfstoffe gegen humanpathogene Retroviren, wie HTLV und HIV, zu entwickeln. Die klassischen Methoden der Impfstoffentwicklung gegen Viren sind bei Retroviren bisher weitestgehend fehlgeschlagen. Daher müssen neue Ansätze ermittelt werden, um erfolgreich Impfstoffe gegen Retroviren herstellen zu können. Wir verwenden ein Mausmodell, die Infektion von Mäusen mit dem „Friend Murine Leukemia Virus“ (FV), um grundlegende immunologische Mechanismen des Impfschutzes gegen Retroviren aufzuklären. Darüber hinaus untersuchen wir, welche Mediatoren des Immunsystems für die Kontrolle einer chronischen Infektion mit Retroviren wichtig sind. Die Erkenntnisse aus diesen Untersuchungen werden verwendet, um neue Immuntherapien und Impfstoffe gegen Retroviren zu entwickeln.

Arbeitsgruppe

Leiter

Prof. Dr. rer. nat. Ulf Dittmer
Tel: +49 (0)201 723 3550
E-Mail: ulf.dittmer@uni-due.de

​​​Dr. rer. nat. Gennadiy Zelinskyy
Tel.: +49 (0)201 723 3541
E-Mail: gennadiy.zelinskyy@uni-due.de

Simone Schimmer, MTA
Tel.: +49 (0)201 723 3583
E-Mail: simone.schimmer@uni-due.de

Tanja Werner, BTA
Tel.: +49 (0)201 723 3583
E-Mail: tanja.werner@uni-due.de

Anna Malyshkina, M. Sc.
Tel.: +49 (0)201 723 3062
E-Mail: anna.malyshkina@uk-essen.de

Alexander Ross, M. Sc.
Tel.: +49 (0)201 723 3042
E-Mail: alexander.ross@uni-due.de

Lucas Otto, M. Sc.
Tel.: +49 (0)201 723 3042
E-Mail: lucas.otto@uni-due.de

Paul David, M. Sc.

Tel.: +49 (0)201 723 3042
E-Mail: paul.david@uni-due.de

 

 

Ausgewählte Publikationen

Schultz BT, Teigler JE, Pissani F, Oster AF, Kranias G, Alter G, Marovich M, Eller MA, Dittmer U, Robb ML, Kim JH, Michael NL, Bolton D, Streeck H. Circulating HIV-Specific Interleukin-21(+)CD4(+) T Cells Represent Peripheral Tfh Cells with Antigen-Dependent Helper Functions. Immunity. 2016 Jan 19;44(1):167-78.

Akhmetzyanova I, Zelinskyy G, Littwitz-Salomon E, Malyshkina A, Dietze KK, Streeck H, Brandau S, Dittmer U. CD137 Agonist Therapy Can Reprogram Regulatory T Cells into Cytotoxic CD4+ T Cells with Antitumor Activity. J Immunol. 2016 Jan 1;196(1):484-92.

Harper MS, Guo K, Gibbert K, Lee EJ, Dillon SM, Barrett BS, McCarter MD, Hasenkrug KJ, Dittmer U, Wilson CC, Santiago ML. Interferon-α Subtypes in an Ex Vivo Model of Acute HIV-1 Infection: Expression, Potency and Effector Mechanisms. PLoS Pathog. 2015 Nov 3;11(11):e1005254.

Akhmetzyanova I, Drabczyk M, Neff CP, Gibbert K, Dietze KK, Werner T, Liu J, Chen L, Lang KS, Palmer BE, Dittmer U, Zelinskyy G. PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8+ T Cell Killing. PLoS Pathog. 2015 Oct 20;11(10):e1005224.

Littwitz-Salomon E, Akhmetzyanova I, Vallet C, Francois S, Dittmer U, Gibbert K. Activated regulatory T cells suppress effector NK cell responses by an IL-2-mediated mechanism during an acute retroviral infection.

Gibbert K, Francois S, Sigmund AM, Harper MS, Barrett BS, Kirchning CJ, Lu M, Santiago ML, Dittmer U. Friend retrovirus drives cytotoxic effectors through Toll-like receptor 3. Retrovirology. 2014 Dec 24;11:126.

Joedicke JJ, Myers L, Carmody AB, Messer RJ, Wajant H, Lang KS, Lang PA, Mak TW, Hasenkrug KJ, Dittmer U. Activated CD8+ T Cells Induce Expansion of Vβ5+ Regulatory T Cells via TNFR2 Signaling. J Immunol. 2014 Sep 15;193(6):2952-60.

Kordelas L, Verheyen J, Beelen DW, Horn PA, Heinold A, Kaiser R, Trenschel R, Schadendorf D, Dittmer U, Esser S; Essen HIV AlloSCT Group. Shift of HIV tropism in stem-cell transplantation with CCR5 Delta32 mutation. N Engl J Med. 2014 Aug 28;371(9):880-2

Dietze KK, Zelinskyy G, Liu J, Kretzmer F, Schimmer S, Dittmer U. Combining regulatory T cell depletion and inhibitory receptor blockade improves reactivation of exhausted virus-specific CD8+ T cells and efficiently reduces chronic retroviral loads. PLoS Pathog. 2013;9(12):e1003798.

Lavender KJ, Pang WW, Messer RJ, Duley AK, Race B, Phillips K, Scott D, Peterson KE, Chan CK,Dittmer U, Dudek T, Allen TM, Weissman IL, Hasenkrug KJ. BLT-humanized C57BL/6 Rag2-/-γc-/-CD47-/- mice are resistant to GVHD and develop B- and T-cell immunity to HIV infection. Blood. 2013 Dec 12;122(25):4013-20.

Littwitz E, Francois S, Dittmer U, Gibbert K. Distinct roles of NK cells in viral immunity during different phases of acute Friend retrovirus infection. Retrovirology. 2013 Nov 1;10:127.

Akhmetzyanova I, Zelinskyy G, Schimmer S, Brandau S, Altenhoff P, Sparwasser T, Dittmer U. Tumor-specific CD4+ T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells. Cancer Immunol Immunother. 2013 Feb;62(2):257-71.

Gibbert K, Joedicke JJ, Meryk A, Trilling M, Francois S, Duppach J, Kraft A, Lang KS, Dittmer U. Interferon-alpha subtype 11 activates NK cells and enables control of retroviral infection. PLoS Pathog. 2012;8(8):e1002868.

Zelinskyy G, Myers L, Dietze KK, Gibbert K, Roggendorf M, Liu J, Lu M, Kraft AR, Teichgräber V, Hasenkrug KJ, Dittmer U. Virus-specific CD8+ T cells upregulate programmed death-1 expression during acute friend retrovirus infection but are highly cytotoxic and control virus replication. J Immunol. 2011 Oct 1;187(7):3730-7.

Dietze KK, Zelinskyy G, Gibbert K, Schimmer S, Francois S, Myers L, Sparwasser T, Hasenkrug KJ,Dittmer U. Transient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8+ T cells and reduces chronic retroviral set points. Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2420-5.

Zelinskyy G, Dietze KK, Hüsecken YP, Schimmer S, Nair S, Werner T, Gibbert K, Kershaw K, Gruber AD, Sparwasser T & Dittmer U. The regulatory T-cell response during acute retroviral infection is locally defined and controls the magnitude and duration of the virus-specific cytotoxic T-cell response. Blood 2009; 114: 3199-3207.

Balkow S, Krux F, Loser K, Becker JU, Grabbe S & Dittmer U. Friend retrovirus infection of myeloid dendritic cells impairs maturation, prolongs contact to naïve T-cells, and favors expansion of regulatory T-cells. Blood 2007; 110: 3949-3958.

Dittmer U, He H, Messer RJ, Schimmer S, Olbrich ARM, Ohlen C, Greenberg PD, Stromnes IM, Iwashiro M, Sakaguchi S, Evans LH, Peterson KE, Yang G & Hasenkrug KJ. Functional impairment of CD8+ T cells by regulatory T cells during persistent retroviral infection. Immunity 2004; 20: 293-303.

Dittmer U, Brooks DM & Hasenkrug KJ. Requirements for multiple lymphocyte subsets in protection by a live-attenuated vaccine against retroviral infection. Nature Medicine 1999; 5:189-193.

Reviews

Gibbert K, Schlaak JF, Yang D, Dittmer U. IFN-α subtypes: distinct biological activities in anti-viral therapy. Br J Pharmacol. 2013 Mar;168(5):1048-58.

Nair S, Bayer W, Ploquin MJ, Kassiotis G, Hasenkrug KJ, Dittmer U.
Distinct roles of CD4+ T cell subpopulations in retroviral immunity: lessons from the Friend virus mouse model. Retrovirology. 2011 Sep 26;8:76.

Li S, Gowans EJ, Chougnet C, Plebanski M & Dittmer U. Natural regulatory T cells and persistent viral infection. Journal of Virology 2008; 82: 21-30.

Hasenkrug J K & Dittmer U. Immune control and prevention of chronic Friend retrovirus infection. Frontiers in Bioscience 2007; 12: 1544-1551.

Schneider-Schaulies S & Dittmer U. Silencing T-cells or T-cell silencing: concepts in virus-induced immunosuppression. Journal of General Virology 2006; 87: 1423-1438.

Dittmer U & Olbrich A R M. Therapeutic treatment of infectious diseases with immunostimulatory oligonucleotides containing CpG motifs. Current Opinion in Microbiology 2003; 6: 472-477.

Hasenkrug KJ & Dittmer U. The role of CD4 and CD8 T-cells in the recovery and protection from retroviral infection: Lessons from the Friend virus model. Virology 2000; 272: 244-249.

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