Project Description

TP17: Contribution of innate immune responses to persistence versus clearance of hepatitis C and hepatitis A virus infections

Hepatitis C virus (HCV) and hepatitis A virus (HAV) share very similar replication strategies. However, HAV infections are always cleared whereas HCV establishes persistence in most cases. The overall aim of this project is to achieve a comprehensive understanding of the mechanisms involved in inducing and counteracting innate immune responses by HAV and HCV, mainly focusing on toll-like receptor 3. Our results will thereby define the key factors responsible for the balanced induction of innate immunity finally determining the establishment of persistent infection of the liver.
Lohmann V, Bartenschlager R. 2019. Indelibly Stamped by Hepatitis C Virus Infection: Persistent Epigenetic Signatures Increasing Liver Cancer Risk. Gastroenterology. 156(8):2130-2133.
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.
Lohmann V. 2018. Hepatitis C virus cell culture models: an encomium on basic research paving the road to therapy development. Med Microbiol Immunol. 2018 Oct 8. doi: 10.1007/s00430-018-0566-x. Review. (Epub ahead of print).
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.e16. doi: 10.1053/j.gastro.2018.03.020.
Klöss V, Grünvogel O, Wabnitz G, Eigenbrod T, Ehrhardt S, Lasitschka F,Lohmann V, Dalpke AH. 2017. Interaction and Mutual Activation of Different Innate Immune Cells Is Necessary to Kill and Clear Hepatitis C Virus-Infected Cells. Front Immunol. 8:1238. doi: 10.3389/fimmu.2017.01238. eCollection 2017.
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 Kinome-wide siRNA Screening. Mol Cell. 65(3):403-415.e8. doi: 10.1016/j.molcel.2016.12.021.
Roth H, Magg V, Uch F, Mutz P, Klein P, Haneke K, Lohmann V, Bartenschlager R, Fackler OT, Locker N, Stoecklin G, Ruggieri A. 2017. Flavivirus Infection Uncouples Translation Suppression from Cellular Stress Responses. MBio. 8(1). pii: e02150-16. doi: 10.1128/mBio.02150-16. Erratum in: MBio. 2017 Apr 18;8(2)
Grünvogel O, Esser-Nobis K, Reustle A, Schult P, Müller B, Metz P, Trippler M, Windisch MP, Frese M, Binder M, Fackler O, Bartenschlager R, Ruggieri A, Lohmann V. 2015. Dead box helicase 60-like (DDX60L) is an interferon stimulated gene restricting hepatitis C virus replication in cell culture. J Virol J Virol. 89:10548-68.
Esser-Nobis K, Harak C, Schult P, Kusov Y, Lohmann V. 2015. Novel perspectives for hepatitis A virus therapy revealed by comparative analysis of hepatitis C virus and hepatitis A virus RNA replication. Hepa- tology 62:397-408
Hiet MS, Bauhofer O, Zayas M, Roth H, Tanaka Y, Schirmacher P, Willemsen J, Grünvogel O, Bender S, Binder M, Lohmann V, Lotteau V, Ruggieri A, Bartenschlager R. Control of temporal activation of hepati- tis C virus-induced interferon response by domain 2 of nonstructural protein 5A. J Hepatol 2015 Apr 20. pii:S0168-8278(15)00298-6. doi: 10.1016/j.jhep.2015.04.015.
Serti E, Werner JM, Chattergoon M, Cox AL, Lohmann V, Rehermann B. 2014. Monocytes activate natu- ral killer cells via inflammasome-induced interleukin 18 in response to hepatitis C virus replication. Gas- troenterology 147: 209-220.
Reiss S, Harak C, Romero-Brey I, Radujkovic D, Klein R, Ruggieri A, Rebhan I, Bartenschlager R, Lohmann V. 2013. The lipid kinase phosphatidylinositol-4 kinase III alpha regulates the phosphorylation status of hepatitis C virus NS5A. PLoS Pathog 9:p e1003359.
Esser-Nobis K, Romero-Brey I, Ganten T M, Gouttenoire J, Harak C, Klein R, Schemmer P, Binder M, Schnitzler P, Moradpour D, Bartenschlager R, Polyak SJ, Stremmel W, Penin F, Eisenbach C, Lohmann V. 2013. Analysis of hepatitis C virus resistance to silibinin in vitro and in vivo points to a novel mecha- nism involving nonstructural protein 4B. Hepatology 57:953-963.
Reiss S, Rebhan I, Backes P, Romero-Brey I, Erfle H, Matula P, Kaderali L, Poenisch M, Blankenburg H, Hiet MS, Longerich T, Diehl S, Ramirez F, Balla T, Rohr K, Kaul A, Buhler S, Pepperkok R, Lengauer T, Albrecht M, Eils R, Schirmacher P, Lohmann V*, Bartenschlager R.* 2011. Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compart- ment. Cell Host Microbe 9: 32-45. *Co-corresponding authors
Jo J, Aichele U, Kersting N, Klein R, Aichele P, Bisse E, Sewell AK, Blum HE, Bartenschlager R, Loh- mann V*, Thimme R*. 2009. Analysis of CD8+ T-cell-mediated inhibition of hepatitis C virus replication using a novel immunological model. Gastroenterology 136:1391-401.*Co-corresponding authors
Binder M, Kochs G, Bartenschlager R, Lohmann V. 2007. Hepatitis C virus escape from the interferon regulatory factor 3 pathway by a passive and active evasion strategy. Hepatology 46:1365-1374.
Quinkert D, Bartenschlager R, Lohmann V. 2005. Quantitative analysis of the hepatitis C virus replication complex. J Virol 79:13594-13605.