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Maternal cytomegalovirus infection: immune activation, transmission, and fetal development
Maternal infection with human cytomegalovirus (CMV) causes maternal immune activation, and the virus can cross the placenta, leading to congenital infection and neurological injuries. This project aims to understand the impact of CMV-induced maternal immune activation on maternal and fetal health and to study the role of Neuropilin-1 in MCMV transmission from mother to fetus.
Hypothesis
Team
Prof. Dr. med., PhD
Felix Stahl
Principal Investigator
Prof. Dr. med.
Wolfram Brune
Principal Investigator
Victoria Tennert
PhD Student
Jendrik Müller
PhD Student
Project-related publications
Muscolino E., Schmitz R., Loroch S., Caragliano E., Schneider C., Rizzato M., Kim Y.H., Krause E., Juranić Lisnić V., Sickmann A., Reimer R., Ostermann E., Brune W. Herpesviruses induce aggregation and selective autophagy of host signalling proteins NEMO and RIPK1 as an immune-evasion mechanism. Nat Microbiol 5, 331-342 (2020).
Deng, Y., Ostermann, E. & Brune, W. A cytomegalovirus inflammasome inhibitor reduces proinflammatory cytokine release and pyroptosis. Nat Commun 15, 786 (2024).
Fonseca Brito L., Tödter S., Kottlau J., Cermann K., Spier A., Petersen E., Schafer I., Twerenbold R., Aepfelbacher M., Lütgehetmann M., Stahl F.R. Performance of an interferon-gamma release assay-based test for cell-mediated immunity to SARS-CoV-2. Front Immunol 14, 1069968 (2023).
Stahl F.R., Heller K., Halle S., Keyser K.A., Busche A., Marquardt A., Wagner K., Boelter J., Bischoff Y., Kremmer E., Arens R., Messerle M., Förster R.. Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung. PLoS Pathog 9, e1003828 (2013).
Tang, J., Frascaroli, G., Lebbink, R.J., Ostermann, E. & Brune, W. Human cytomegalovirus glycoprotein B variants affect viral entry, cell fusion, and genome stability. Proc Natl Acad Sci U S A 116, 18021-18030 (2019).
Cimato, G., Zhou, X., Brune, W. & Frascaroli, G. Human cytomegalovirus glycoprotein variants governing viral tropism and syncytium formation in epithelial cells and macrophages. J Virol 98, e0029324 (2024).
Stahl F.R., Keyser K.A., Heller K., Bischoff Y., Halle S., Wagner K., Messerle M., Förster R. Mck2-dependent infection of alveolar macrophages promotes replication of MCMV in nodular inflammatory foci of the neonatal lung. Mucosal Immunol 8, 57-67 (2015).
Halle S., Keyser K.A., Stahl F.R. et al. In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity. Immunity 44, 233-45 (2016).
Stahl F.R., Jung R., Jazbutyte V., Ostermann E., Tödter S., Brixel R., Kemmer A., Halle S., Rose-John S., Messerle M., Arck P.C., Brune W., Renne T.. Laboratory diagnostics of murine blood for detection of mouse cytomegalovirus (MCMV)-induced hepatitis. Sci Rep 8, 14823 (2018).
Brito L.F., Ostermann E., Perez A., Tödter S., Virdi S., Indenbirken D., Glau L., Gieras A., Brixel R., Arens R., Grundhoff A., Arck P., Diemert A., Tolosa E., Brune W., Stahl R.F. Limited protection against early-life cytomegalovirus infection results from deficiency of cytotoxic CD8 T cells. bioRxiv, 2024.07.10.602923 (2024).