Viral evolution is a central research focus of our team. RNA viruses such as hepatitis E virus or enteroviruses exhibit remarkable genetic variability. This diversity arises from error-prone replication, recombination, and host-driven selection.

We investigate how viruses evolve within individual hosts and across broader timescales—such as during zoonotic transmission or the emergence of antiviral resistance. Using high-throughput sequencing and computational tools, we analyze viral diversity, reconstruct phylogenetic relationships, and identify selective pressures.

Our goal is to uncover evolutionary patterns that contribute to viral pathogenesis and therapeutic failure.

Viruses profoundly reshape the cellular biology of their hosts. Our group explores how infections alter immune signaling, interfere with defense pathways, and trigger inflammatory responses.

We study how acute and chronic infections shift the balance between immune activation and suppression—and how this impacts disease progression and viral persistence. A particular focus lies on regulatory networks that either promote or restrict antiviral functions.

Our goal is to pinpoint functional control hubs within the virus–host interface that may serve as targets for novel therapeutic strategies.

Infections affect biological systems on multiple levels—from gene expression in individual cells to complex changes across entire tissues. Our aim is to capture these dynamics in a comprehensive way.

We integrate bulk, single-cell, and spatial transcriptomics with proteomic approaches and advanced analytical methods. This multilayered strategy allows us to reconstruct infection trajectories in space and time, decode cell type-specific responses, and uncover systemic patterns of viral pathogenesis.

Our research provides high-resolution insights into all layers of infection—from molecular signaling to cellular networks and tissue architecture. The result: novel hypotheses on virus–host interactions and rich data resources for targeted intervention strategies.

Group Leader: Dr. Richard JP Brown

Viruses are obligate intracellular parasites, hijacking and reprogramming host cells to enable the propagation and dissemination of their progeny: the viral life cycle therefore represents a complex and multistage interplay of virally encoded proteins interacting with host proteins. Host dependency factors facilitate viral spread and are essential at every step of the virus lifecycle including attachment, entry, uncoating, genome translation, replication, assembly and release. In parallel, the cellular antiviral response to infection, which can actively suppress viral propagation by multiple diverse mechanisms, is mediated by host restriction factors. Host restriction factors can be constitutively expressed or induced upon infection as part of the interferon system. Viral species and tissue tropism are therefore governed by a finely tuned balance between host dependency and restriction factors.

In the Virus Tropism research group, we focus on viruses that cause severe disease in humans. Utilizing -omics approaches coupled with in vitro experimental systems, we identify and characterize host determinants of viral species and tissue tropism. Furthermore, we investigate host transcriptional responses to an array of viral infections, to dissect and compare global cellular antiviral programs in different tissues/species. Our research aims to improve understanding of the viral life cycle, shed light on pathogenesis mechanisms and the determinants of tissue/species tropism, and to ultimately identify potential druggable therapeutic targets in the host.

Selected Publications:

Qu B, Miskey C, Gömer A, Kleinert RDV, Calvo-Ibanez S, Eberle R, Ebenig A, Postmus D, Nocke MK, Herrmann M, Itotia TK, Herrmann ST, Heinen N, Höck S, Hastert FD, von Rhein C, Schürmann C, Li X, van Zandbergen G, Widera M,  Ciesek S, Schnierle BS, Tarr AW, Steinmann E, Goffinet C, Pfaender S, Krijnse-Locker J, Mühlebach MD, Todt D, Brown RJP (2024)
‘TMPRSS2-mediated SARS-CoV-2 uptake boosts innate immune activation, enhances cytopathology, and drives convergent virus evolution’
PNAS. 121 (23): e2407437121
https://www.pnas.org/doi/full/10.1073/pnas.2407437121

Heinen N, Khanal R, Westhoven S, Klöhn M, Herrmann ST, Herrmann M, Tuoc T, Ulmke PA, Nguyen HD, Nguyen HP, Steinmann E, Todt D, Brown RJP, Sharma AD, Pfaender S (2023)
‘Productive infection of primary human hepatocytes with SARS-CoV-2 induces antiviral and proinflammatory responses’
Gut 2024: 73:e14
https://doi.org/10.1136/gutjnl-2023-330961

Ebenig A, Muraleedharan S, Kazmierski J, Todt D, Auste A, Anzaghe M, Gömer A, Postmus D, Gogesch P, Niles M, Plesker R, Miskey C, Gellhorn-Serra M, Breithaupt A, Hörner C, Kruip C, Ehmann R, Ivics Z, Waibler Z, Pfaender S, Wyler E, Landthaler M, Kupke A, Nouailles G, Goffinet C, Brown RJP, Mühlebach MD (2022)
‘Vaccine-associated enhanced respiratory pathology in COVID-19 hamsters after T_H2-biased immunization’
Cell Reports 40(7): 111214
https://doi.org/10.1016/j.celrep.2022.111214

Tegtmeyer B, Vieyres G, Todt D, Lauber C, Ginkel C, Engelmann M, Herrmann M, Pfaller CK, Vondran FWR, Broering R, Vafadarnejad E, Saliba AE, Puff C, Baumgärtner W, Miskey C, Ivics Z, Steinmann E, Pietschmann T, Brown RJP (2021)
‘Initial HCV infection of adult hepatocytes triggers a temporally structured transcriptional program containing diverse pro- and anti-viral elements’
Journal of Virology 95(10): e00245-21
https://doi.org/10.1128/JVI.00245-21

Brown RJP, Tegtmeyer B, Sheldon J, Khera T, Kusuma A, Todt D, Vieyres G, Weller R, Joecks S, Zhang Y, Wiechert S, Bankwitz D, Welsch K, Ginkel C, Engelmann M, Gerold G, Steinmann E, Yuan Q, Ott M, Vondran FWR, Krey T, Stroeh LJ, Miskey C, Ivics Z, Herder V, Baumgärtner W, Lauber C, Seifert M, Tarr AW, McClure CP, Randall G, Baktash Y, Ploss A, Dao Thi VL, Michailidis E, Saeed M, Verhoye L, Meuleman P, Goedeke N, Wirth D, Rice CM**, Pietschmann T (2020)
‘Liver expressed Cd302 and Cr1l limit hepatitis C virus cross species transmission to mice’
Science Advances 6(45): eabd3233
https://doi.org/10.1126/sciadv.abd3233