Project Description
Public­ations

TP09: Control of hepatitis C virus infection by the interferon system and virus – host co-evolution

A hallmark of hepatitis C virus (HCV) infections is the high propensity to establish persistence. This is achieved by active suppression and perturbation of both innate and adaptive immune responses. However the mechanistic details are still poorly understood and the relative contributions of the various immune escape strategies for persistence are unknown. Here we want to address three complementary aspects: (i) how LGP2 modulates RIG-I and MDA5 triggered IFN responses, (ii) how HCV persists in IFN-activated cells and (iii) the long-term co-evolution of hepatitis viruses with their hosts.
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)
Seitz S, Habjanič J, Schütz AK, Bartenschlager R. 2020. The Hepatitis B Virus Envelope Proteins: Molecular Gymnastics Throughout the Viral Life Cycle. 2020. Annu Rev Virol. 2020 Jun 29. doi: 10.1146/annurev-virology-092818-015508 (TP09,TP23)
Che C Colpitts, Ridewood S., Schneiderman B., Warne J., Tabata K., Caitlin F Ng, Bartenschlager R, Selwood DL, Towers. GJ 2020. Hepatitis C virus exploits cyclophilin A to evade PKR. eLife. 2020; 9: e52237. doi: 10.7554/eLife.52237 (TP09)
Stanifer ML, Kee C, Cortese M, Zumaran CM, Triana S, Mukenhirn M, Kraeusslich HG, Alexandrov T, Bartenschlager R, Boulant S. 2020. Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells. Cell Rep. 2020 Jul 7;32(1):107863. doi: 10.1016/j.celrep.2020.107863 (TP09, TP22)
Kinast V, Plociennikowska A, Anggakusuma, Bracht T, Todt D, Brown RJ, Boldanova T, Zhang Y, Brueggemann Y, Friesland M, Engelmann M, Vieyres G, Broering R, Vondran FWR, Heim MH, Sitek B, Bartenschlager R, Pietschmann T, Steinmann E. 2020. C19orf66 is an interferon-induced inhibitor of HCV replication that restricts formation of the viral replication organelle. J Hepatol. 2020 Apr 12. pii: S0168-8278(20)30209-9. doi: 10.1016/j.jhep.2020.03.047. (TP09)
A Lee JY, Cortese M, Haselmann U, Tabata K, Romero-Brey I, Funaya C, Schieber NL, Qiang Y, Barten-schlager M, Kallis S, Ritter C, Rohr K, Schwab Y, Ruggieri A, Bartenschlager R. 2019. Spatiotemporal Coupling of the Hepatitis C Virus Replication Cycle by Creating a Lipid Droplet- Proximal Membranous Replication Compartment. Cell Rep. 18;27(12):3602-3617.e5..
B Zhang Z, Filzmayer C, Ni Y, Sültmann H, Mutz P, Hiet MS, Vondran FWR, Bartenschlager R, Urban S. 2018. Hepatitis D Virus replication is sensed by MDA5 and induces IFN-β/λ responses in hepatocytes. J Hepatol. 69(1):25-35.
C Grünvogel O, Colasanti O, Lee JY, 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 Reduces Activation of Toll Like Receptor 3 in Hepatocytes. Gastroenterology. 154(8):2237-2251.
D 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 Pro-tect HCV From Antiviral Activity of Interferon. Gastroenterology. 154(6):1791-1804.
E Pollmann J, Götz JJ, Rupp D, Strauss O, Granzin M, Grünvogel O, Mutz P, Kramer C, Lasitschka F, Lohmann V, Björkström NK, Thimme R, Bartenschlager R, Cerwenka A. 2018. Hepatitis C virus-induced natural killer cell proliferation involves monocyte-derived cells and the OX40/OX40L axis. J Hepatol. 68(3):421-430.
F Lauber C, Seitz S, Mattei S, Suh A, Beck J, Herstein J, Börold J, Salzburger W, Kaderali L, Briggs J, Bartenschlager R. 2017. Deciphering the origin and evolution of hepatitis B viruses by means of a family of nonenveloped fish viruses. Cell Host & Microbe, 22(3):387-399.e6.
G Harak C, Meyrath M, Romero-Brey I, Schenk C, Gondeau C, Schult P, Esser-Nobis K, Saeed M, Ned-dermann P, Schnitzler P, Gotthardt D, Perez-Del-Pulgar S, Neumann-Haefelin C, Thimme R, Meuleman P, Vondran FW, Francesco R, Rice CM, Bartenschlager R, Lohmann V. 2017. Tuning a cellular lipid ki-nase activity adapts hepatitis C virus to replication in cell culture. Nature Microbiology 23;2:17012.
H Pfaender S, Walter S, Grabski E, Todt D, Bruening J, Romero-Brey I, Gather T, Brown RJ, Hahn K, Puff C, Pfankuche VM, Hansmann F, Postel A, Becher P, Thiel V, Kalinke U, Wagner B, Bartenschlager R, Baumgärtner W, Feige K, Pietschmann T, Cavalleri JM, Steinmann E. 2017. Immune protection against reinfection with nonprimate hepacivirus. Proc Natl Acad Sci U S A. 114(12):E2430-E2439.
I Willemsen J, Wicht O, Wolanski JC, Baur N, Bastian S, Haas DA, Matula P, Knapp B, Meyniel-Schicklin L, Wang C, Bartenschlager 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 Ki-nome-wide siRNA Screening. Molecular Cell. 65(3):403-415.
J Senís E, Mockenhaupt S, Rupp D, Bauer T, Paramasivam N, Knapp B, Gronych J, Grosse S, Windisch MP, Schmidt F, Theis FJ, Eils R, Lichter P, Schlesner M, Bartenschlager R, Grimm D. 2016. TALEN/CRISPR-mediated engineering of a promoterless anti-viral RNAi hairpin into an endogenous miRNA locus. Nucleic Acids Research 45(1):e3.