Project Description
Public­ations

TP11: Effects of persistent antiviral signalling on tissue homeostasis and antiviral immunity

The cell-intrinsic antiviral system is highly potent, but imposes a massive perturbation onto cellular homeostasis, which is why it evolved to be strictly acute and transient. We investigate the consequences of prolonged stimulation of this defence program, as it occurs in the course of persistent virus infection, such as HCV. We examine both, the virus infected cell itself (counter regulation, refractoriness), as well as the effects of the cytokines, which it continuously secretes, onto non-infected neighbouring cells and onto cells of the immune system. We will address how this inflammatory milieu might contribute to the establishment of persistence of the viral infection.
Schulien I, Kemming J, Oberhardt V, Wild K, Seidel LM, Killmer S, Sagar, Daul F, Salvat Lago M, Decker A, Luxenburger H, Binder B, Bettinger D, Sogukpinar O, Rieg S, Panning M, Huzly D, Schwemmle M, Kochs G, Waller CF, Nieters A, Duerschmied D, Emmerich F, Mei HE, Schulz AR, Llewellyn-Lacey S, Price DA, Boettler T, Bengsch B, Thimme R, Hofmann M, Neumann-Haefelin C. Characterization of pre-existing and induced SARS-CoV-2-specific CD8+ T cells. Nat Med. 2020 Nov 12. doi: 10.1038/s41591-020-01143-2. (TP01, TP02, TP11, TP20, TP21)
Robichon K, Maiwald T, Schilling M, Schneider A, Willemsen J, Salopiata F, Teusel M, Kreutz C, Ehlting C, Huang J, Chakraborty S, Huang X, Damm G, Seehofer D, Lang PA, Bode JG, Binder M, Bartenschlager R, Timmer J, Klingmüller U. Identification of Interleukin1β as an Amplifier of Interferon alpha-induced Antiviral Responses. PLoS Pathog. 2020 Oct 1;16(10):e1008461. doi: 10.1371/journal.ppat.1008461. (TP09, TP10, TP11)
Urban C, Welsch H, Heine K, Wüst S, Haas DA, Dächert C, Pandey A, Pichlmair A, Binder M. Persistent Innate Immune Stimulation Results in IRF3-Mediated but Caspase-Independent Cytostasis. Viruses. 2020 Jun 11;12(6):635. doi: 10.3390/v12060635. (TP11)
Lampl S, Janas MK, Donakonda S, Brugger M, Lohr K, Schneider A, Manske K, Sperl LE, Kläger S, Küster B, Wettmarshausen J, Müller C, Laschinger M, Hartmann D, Hüser N, Perocchi F, Schmitt-Kopplin P, Hagn F, Zender L, Hornung V, Borner C, Pichlmair A, Kashkar H, Klingenspor M, Prinz M, Schreiner S, Conrad M, Jost PJ, Zischka H, Steiger K, Krönke M, Zehn D, Protzer U, Heikenwälder M, Knolle PA, Wohlleber D. Reduced mitochondrial resilience enables non-canonical induction of apoptosis after TNF receptor signaling in virus-infected hepatocytes. J Hepatol. 2020 Jun 26:S0168-8278(20)30398-6. doi: 10.1016/j.jhep.2020.06.026. (TP05, TP06, TP10, TP11, TP13, TP16, TP18)
Namineni S, O'Connor T, Faure-Dupuy S, Johansen P, Riedl T, Liu K, Xu H, Singh I, Shinde P, Li F, Pandyra A, Sharma P, Ringelhan M, Muschaweckh A, Borst K, Blank P, Lampl S, Durantel D, Farhat R, Weber A, Lenggenhager D, Kündig TM, Staeheli P, Protzer U, Wohlleber D, Holzmann B, Binder M, Breuhahn K, Assmus LM, Nattermann J, Abdullah Z, Rolland M, Dejardin E, Lang PA, Lang KS, Karin M, Lucifora J, Kalinke U, Knolle PA, Heikenwalder M. 2020. A dual role for hepatocyte-intrinsic canonical NF-κB signaling in virus control. J Hepatol. 72(5):960-975. (TP05, TP06, TP11, TP13, TP14)
Binder B, Thimme R. CD4+ T cell responses in human viral infection: lessons from hepatitis C. J Clin Invest. 2020 Feb 3;130(2):595-597. doi: 10.1172/JCI133222. (TP01, TP11)
A. Cadena C, Ahmad S, Xavier A, Willemsen J, Park S, Park JW, Oh SW, Fujita T, Hou F, Binder M, Hur S. 2019. Ubiquitin-Dependent and -Independent Roles of E3 Ligase RIPLET in Innate Immunity. Cell. 177(5):1187–1200
B. Hubel P, Urban C, Bergant V, Schneider WM, Knauer B, Stukalov A, Scaturro P, Mann A, Brunotte L, Hoffmann HH, Scho-ggins JW, Schwemmle M, Mann M, Rice CM, Pichlmair, A. 2019. A protein interaction network of interferon stimulated genes extends the innate immune system landscape. Nat Immunol. 20(4):493–502
C. Scaturro P, Stukalov A, Haas DA, Cortese M, Draganova K, Płaszczyca A, Bartenschlager R, Götz M, Pichlmair A. 2018. An orthogonal proteomic survey uncovers novel Zika virus host factors. Nature 561(7722):253-257.
D. Grünvogel O, Colasanti O, Lee J-Y, Klöss V, Belouzard S, Reustle A, Esser-Nobis K, Hesebeck-Brinckmann J, Mutz P, Hoffmann K, Mehrabi A, Koschny R, Vondran FWR, Gotthardt D, Schnitzler P, Neumann-Haefelin C, Thimme R, Binder M, Bartenschlager R, Dubuisson J, Dalpke AH, Lohmann V. 2018. Secretion of Hepatitis C Virus Replication Intermediates Re-duces Activation of Toll-Like Receptor 3 in Hepatocytes. Gastroenterology 154(8):2237–2251.e16.
E. Mutz P, Metz P, Lempp FA, Bender S, Qu B, Schöneweis K, Seitz S, Tu T, Restuccia A, Frankish J, Dächert C, Schusser B, Koschny R, Polychronidis G, Schemmer P, Hoffmann K, Baumert TF, Binder M, Urban S, Bartenschlager R. 2018. HBV Bypasses the Innate Immune Response and Does Not Protect HCV From Antiviral Activity of Interferon. Gastroenterology 154(6):1791–1804.e22.
F. Haas DA, Meiler A, Geiger K, Vogt C, Preuss E, Kochs G, Pichlmair A. 2018. Viral targeting of TFIIB impairs de novo poly-merase II recruitment and affects antiviral immunity. PLoS Pathogens 14(4):e1006980.
G. Holze C, Michaudel C, Mackowiak C, Haas DA, Benda C, Hubel P, Pennemann FL, Schnepf D, Wettmarshausen J, Braun M, Leung DW, Amarasinghe GK, Perocchi F, Staeheli P, Ryffel B, Pichlmair A. 2018. Oxeiptosis, a ROS-induced caspase-independent apoptosis-like cell-death pathway. Nat Immunol. 19(2):130-140.
H. Goonawardane N, Gebhardt A, Bartlett C, Pichlmair A, Harris M. 2017. Phosphorylation of Serine 225 in Hepatitis C Virus NS5A Regulates Protein-Protein Interactions. J Virol 91(17):e00805-17
I. Willemsen J, Wicht O, Wolanski JC, Baur N, Bastian S, Haas DA, Matula P, Knapp B, Meyniel-Schicklin L, Wang C, Barten-schlager R, Lohmann V, Rohr K, Erfle H, Kaderali L, Marcotrigiano J, Pichlmair A, Binder M. 2017. Phosphorylation-Dependent Feedback Inhibition of RIG-I by DAPK1 Identified by Kinome-wide siRNA Screening. Mol Cell. 65(3):403-415.e8.
J. Grünvogel O, Esser-Nobis K, Windisch MP, Frese M, Trippler M, Bartenschlager R, Lohmann V, Binder M. 2016. Type I and type II interferon responses in two human liver cell lines (Huh-7 and HuH6). Genomics Data 7:166-70