Steffen Lab – Faculty Research – College of Veterinary Medicine and Biomedical Sciences

Steffen Lab

Our lab investigates emerging zoonotic RNA viruses, with a focus on neurotropic flaviviruses that cause severe disease in some hosts while others remain asymptomatic. We study how viral, host, and vector-derived factors interact to shape infection outcomes, immune evasion, and pathogenesis. Using human monocyte-derived dendritic cells and iPSC-derived neuronal cells, we dissect how secreted viral proteins, such as the flavivirus non-structural protein 1, modulate immune signaling in the periphery and in the central nervous system during neuroinvasive infection.

We also examine how tick saliva and viral factors cooperate to promote transmission and immune evasion at the vector bite site. To support these efforts, we use a mammalian protein expression and purification system to generate recombinant glycoproteins for functional and mechanistic studies. Our goal is to define key molecular interactions that can guide the development of targeted immunotherapeutic strategies to prevent systemic spread and virus-induced central nervous system damage.

The Steffen Lab is part of the Center for Vector-Borne Infectious Diseases.

research project

The Impact of Secreted Orthoflavivirus NS1 Proteins on Immune Signaling and Viral Spread in Central Nervous System Cells

Neuroinvasive flaviviruses, such as West Nile and Powassan viruses, cause encephalitis by disrupting the immune environment in the central nervous system. We investigate the unexplored role of the viral secreted non-structural protein 1 in modulating immune responses in the CNS during flavivirus infection. Addressing this knowledge gap is critical for the development of new therapeutic strategies.

research project

Redirecting Immune Responses at the Vector Inoculation Site to Prevent Tick-Borne Flavivirus Infection

Tick-borne flaviviruses can cause encephalitis and long-term neurological damage. They are transmitted by ticks during a prolonged feeding process that can last several days. This extended timeline can be exploited for targeted intervention. We work on novel immunotherapeutic approaches that redirect immune responses at the tick bite site to prevent viral amplification and systemic dissemination.

research project

Defining the Immunomodulatory Landscape of Tickborne Flavivirus Transmission

We investigate how tick saliva and secreted viral proteins contribute to the transmission and immune modulation of tick-borne flaviviruses. We compare salivary components between infected and uninfected ticks and assess how these components impact immune activation. This work will uncover how viral and vector-derived factors cooperate to shape infection outcomes and disease severity.

Publications

Tetraspanins 10 and 15 support Venezuelan equine encephalitis virus replication in astrocytoma cells
Mara Duven, Alina Friedrichs, Michael G Tomlinson, Imke Steffen, Gisa Gerold (2025) Molecular biology of the cell. Vol.36(3) ISSN: 1059-1524 , 1939-4586; DOI: 10.1091/mbc.E24-12-0574

Poor virus-specific T-cell responses early after tick-borne encephalitis virus infection correlate with disease severity.
Aregay, A., Slunečko, J., Bogovic, P., Korva, M., Resman Rus, K., Knap, N., … Rimmelzwaan, G. F. (2024). Emerging Microbes & Infections, 13(1). https://doi.org/10.1080/22221751.2024.2317909

Tick-borne encephalitis vaccine breakthrough infections induce aberrant T cell and antibody responses to non-structural proteins.
Aregay, A., Slunečko, J., Korva, M. et al. npj Vaccines 9, 141 (2024). https://doi.org/10.1038/s41541-024-00936-7

West Nile and Usutu viruses are efficiently inactivated in platelet concentrates by UVC light using the THERAFLEX UV-Platelets system.
Gravemann U, Boelke M, Könenkamp L, Söder L, Maurer M, Ziegler U, et al. Vox Sang. 2024; 119: 827–833.