Project Description
Publications
TP17: Contribution of innate immune responses to persistence versus clearance of hepatitis C and hepatitis A virus infections
We study the role of ESCRT in dsRNA secretion and unravel the cellular determinants of HCV recognition by TLR3. For HAV, we aim to identify protease-independent mechanism(s) blunting the cell intrinsic innate immunity in vivo and in vitro, with a focus on the viral protein 2B. Finally, we will study the contribution of viral replication fitness on the outcome of HCV and HAV infections. Our results will ultimately disentangle the complex relationship between viral replication, immune induction and counteraction goverining persistence versus clearance of hepatotropic viruses.. Grunvogel O, Colasanti O, Lee JY, Kloss 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, 2237-2251 e2216. doi:10.1053/j.gastro.2018.03.020.Colasanti O, Burm R, Huang HE, Riedl T, Traut J, Gillich N, Li TF, Corneillie L, Faure-Dupuy S, Grunvogel O, Heide D, Lee JY, Tran CS, Merle U, Chironna M, Vondran FWR, Esser-Nobis K, Binder M, Bartenschlager R, Heikenwalder M, Meuleman P, Lohmann V. (2023) Comparison of HAV and HCV infections in vivo and in vitro reveals distinct patterns of innate immune evasion and activation. J Hepatol. doi:10.1016/j.jhep.2023.04.023.Heuss C*, Rothhaar P*, Burm R, Lee JY, Ralfs P, Haselmann U, Stroh LJ, Colasanti O, Tran CS, Schafer N, Schnitzler P, Merle U, Bartenschlager R, Patel AH, Graw F, Krey T, Laketa V, Meuleman P, Lohmann V. (2022) A Hepatitis C virus genotype 1b post-transplant isolate with high replication efficiency in cell culture and its adaptation to infectious virus production in vitro and in vivo. PLoS Pathog. 18, e1010472. doi:10.1371/journal.ppat.1010472.Jo J, Aichele U, Kersting N, Klein R, Aichele P, Bisse E, Sewell AK, Blum HE, Bartenschlager R, Lohmann V*, Thimme R.* (2009) Analysis of CD8+ T-cell-mediated inhibition of hepatitis C virus replication using a novel immunological model. Gastroenterology. 136, 1391-1401. doi: 10.1053/j.gastro.2008.12.034.Pollmann J, Gotz JJ, Rupp D, Strauss O, Granzin M, Grunvogel O, Mutz P, Kramer C, Lasitschka F, Lohmann V, Bjorkstrom 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, 421-430. doi:10.1016/j.jhep.2017.10.021.Kloss V, Grunvogel 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.2017.01238.14. Chen P*, Wojdyla JA*, Colasanti O*, Li Z, Qin B, Wang M, Lohmann V*, Cui S.* (2022) Biochemical and structural characterization of hepatitis A virus 2C reveals an unusual ribonuclease activity on single-stranded RNA. Nucleic Acids Res. 50, 9470-9489. doi:10.1093/nar/gkac671.Harak C, Meyrath M, Romero-Brey I, Schenk C, Gondeau C, Schult P, Esser-Nobis K, Saeed M, Neddermann P, Schnitzler P, Gotthardt D, Perez-Del-Pulgar S, Neumann-Haefelin C, Thimme R, Meuleman P, Vondran FW, De Francesco R, Rice CM, Bartenschlager R, Lohmann V. (2016) Tuning a cellular lipid kinase activity adapts hepatitis C virus to replication in cell culture. Nat Microbiol. 2, 16247. doi:10.1038/nmicrobiol.2016.247.20. Costa R , Todt D, Zapatero-Belinchon F, Schenk C, Anastasiou OE, Walker A, Hertel B, Timmer L, Bojkova D, Ruckert M, Sarrazin C, Timm J, Lohmann V, Manns MP, Steinmann E, von Hahn T, Ciesek S. (2019) SEC14L2, a lipid-binding protein, regulates HCV replication in culture with inter- and intra-genotype variations. J Hepatol. 70, 603-614. doi:10.1016/j.jhep.2018.11.012.Chen Q, Coto-Llerena M, Suslov A, Teixeira RD, Fofana I, Nuciforo S, Hofmann M, Thimme R, Hensel N, Lohmann V, Ng CKY, Rosenberger G, Wieland S, Heim MH. (2021) Interferon lambda 4 impairs hepatitis C viral antigen presentation and attenuates T cell responses. Nat Commun. 12, 4882. doi:10.1038/s41467-021-25218-x.