Viral infection after solid organ or stem cell transplantation

Project leader:

Patients with an immunodeficiency, and in particular transplant recipients, have a reduced ability to control infectious agents. In the presence of a diminished functional T cell response, a substantial proportion of individuals who were previously infected with EBV cannot prevent infected B cells from resuming proliferation (Figure 1 and 2). Transplant recipients, in particular children, who undergo primary infection whilst already under immunosuppressive treatment carry an even higher risk of EBV-associated diseases like post-transplant lymphoproliferative disorders (PTLD). We have previously studied the viral strains that are found in EBV-associated nasopharyngeal carcinomas and gastric carcinomas and found that these strains exhibit specific properties (Tsai et al. Cell reports 2013, Shumilov, Tsai et al Nature comm. 2017). We are now exploring the hypothesis that the risk of PTLD is linked with infections with EBV strains endowed with higher transforming abilities. We have recruited a collective of patients with EBV reactivation after transplantation and have established cell lines infected with EBV from their peripheral blood. We aim to study multiple parameters such as viral and cellular protein implicated in EBV-mediated transformation and microRNA expression in primary cells and in the cell lines that were established from these patients.

 

This project results from a close cooperation with the Kidney Center Heidelberg e.v., the Department of Haematology as well as the Institute of Virology from the University of Heidelberg.



Figure 1: Transplant recipients are at risk of EBV-mediated lymphoproliferations. Top panel: EBV infected-cells in the peripheral blood of a transplant recipient stained by MGG. Bottom panel: in situ hybridization with a probe specific for the EBV non-coding RNAs EBER. Peripheral blood cells (PBMC) from a transplant recipient were stained for EBER. B cells were immunopurified with a CD19 specific antibody and the EBER staining was performed on CD19-positive and CD19-negative cells.
© dkfz.de

Figure 2: EBV genomes in B cells from a transplant recipient. We performed chromosome FISH to visualize the EBV DNA in infected cells. The pictures show cells undergoing lytic replication or latently infected cells with a varying number of viral episomes.
© dkfz.de

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