Mar­co Binder, Ph.D.

m.binder@dkfz.de

Phone: ++49-(0)6221–42-4974

Dynamics of Early Viral Infection and the Innate Antiviral Response

Projects

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.

For detailed infor­ma­tion on our research lines, please vis­it our web­site at the DKFZ:
https://www.dkfz.de/en/virus-assoziierte-karzinogenese/groups/AGBinder/research.html

Selected Publications

Com­plete pub­li­ca­tion list (PubMed)

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