Marco Binder, Ph.D.
Dynamics of Early Viral Infection and the Innate Antiviral Response
Our research group focuses on the very early interactions of viruses and their host cell. As most cells have very potent cell-intrinsic defense mechanisms in place, viruses require replication strategies to either outrun the cellular antiviral response, or to actively antagonize those defense mechanisms, or both. In the vast majority of cases, this race ends with clear winner– either the virus succeeds and ultimately kills the cell, liberating countless offspring viruses, or the innate immune pathways prevail eventually clearing the virus from the infected cell. The most intriguing case may, however, be the rare situation in which both adversaries reach a balance, allowing the infection to persist for long periods of time (up to decades in the case of Hepatitis C virus).
We study the molecular mechanisms behind pathogen recognition and subsequent antiviral signaling in the context of model viruses and systems that can stringently controlled. Our models include, amongst others, Influenza A virus (IAV), Rift valley fever virus (RVFV) or virus-free stimulation of the cellular antiviral system by transfection of ligand RNAs or constitutively active signaling molecules. With molecular and cell biological as well as biochemical techniques we dissect the cellular pathways leading to the induction of type I and III interferons in addition to the proinflammatory system. We then apply modern systems biological approaches and mathematical modeling to integrate this knowledge into a comprehensive framework of interactions. This will be particularly essential for the understanding of the complex inter-dependencies between the virus and its host cell in the course of establishing a persistent infection. Persistent infection and the accompanying lasting (chronic) inflammatory response are furthermore critical determinants for the eventual initiation of cancer development, e.g. in Hepatitis C infections.
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, pii: S0092-8674(19)30279‑X (ePub ahead of print)
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
Stanifer ML, Rippert A, Kazakov A, Willemsen J, Bucher D, Bender S, Bartenschlager R, Binder M, Boulant S. (2016) Reovirus intermediate subviral particles constitute a strategy to infect intestinal epithelial cells by exploiting TGF‑β dependent pro-survival signaling. Cell. Microbiol. 18(12):1831–1845
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). Genom. Data 7:166–70
Bender S, Reuter A, Eberle F, Einhorn E, Binder M, Bartenschlager R. (2015) Activation of Type I and III Interferon Response by Mitochondrial and Peroxisomal MAVS and Inhibition by Hepatitis C Virus. PLoS Pathog. 11(11):e1005264
Trotard M, Tsopoulidis N, Tibroni N, Willemsen J, Binder M, Ruggieri A, Fackler OT. (2015) Sensing of HIV‑1 Infection in Tzm-bl Cells with Reconstituted Expression of STING. J. Virol. 90(4):2064–76
Binder M, Sulaimanov N, Clausznitzer D, Schulze M, Hüber CM, Lenz SM, Schlöder JP, Trippler M, Bartenschlager R, Lohmann V, Kaderali L. (2013) Replication vesicles are load- and choke-points in the hepatitis C virus lifecycle. PLoS Pathog. 9(8):e1003561
Pichlmair A, Kandasamy K, Alvisi G, Mulhern O, Sacco R, Habjan M, Binder M, Stefanovic A, Eberle CA, Goncalves A, Bürckstümmer T, Müller AC, Fauster A, Holze C, Lindsten K, Goodbourn S, Kochs G, Weber F, Bartenschlager R, Bowie AG, Bennett KL, Colinge J, Superti-Furga G. (2012) Viral immune modulators perturb the human molecular network by common and unique strategies. Nature 487(7408):486–90
Binder M, Eberle F, Seitz S, Mücke N, Hüber CM, Kiani N, Kaderali L, Lohmann V, Dalpke A, Bartenschlager R. (2011) olecular mechanism of signal perception and integration by the innate immune sensor retinoic acid-inducible gene‑I (RIG‑I). J Biol. Chem. 286(31):27278–87
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(5):1365–74
Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J. (2005) Cardif is an adaptor protein in the RIG‑I antiviral pathway and is targeted by hepatitis C virus. Nature 437(7062):1167–72