Division of Pathogenesis of Virus Associated Tumors
Prof. Dr. Dr. Henri-Jacques Delecluse
Our research projects focus on the pathogenesis of cancers caused by an infection with the Epstein-Barr virus (EBV) and on the development of strategies to prevent them.
EBV is aetiologically linked with 2% of all malignant tumours worldwide. Hence, a very substantial number of cancers could be prevented by vaccination against this virus. Our research interests are focused on the molecular mechanisms that allow multiplication, infection and ultimately malignant transformation of B cells and epithelial cells. The large size of the viral genome precludes the use of conventional cloning techniques; instead we have developed a genetic system that allows modification of every single base pair within the viral genome. Over the years we have used this technology to construct a large panel of viral mutants that lack genes involved in multiple virus functions. More recently, we have focused our attention on viral non-coding RNAs, such as microRNAs. We are also interested in studying the phenotypic traits of EBV strains isolated in different areas of the world. These projects make extensive use of large-scale genomics and Bioinformatics approaches that are available in the DKFZ core facility. In addition, we are developing custom software to integrate our data with the manifold information available on virus-host interactions.
We have also generated mutants that could be potentially used as vaccines. Indeed, these produce large amounts of viral DNA-free virus-like particles (VLPs). These particles elicit a strong immune response, yet have lost any pathogenic potential. This approach has been taken further to develop a new type of armed antibody that consists of fusion proteins between antibodies and EBV epitopes. These chimeric antibodies lead to efficient and specific presentation of EBV-specific antigens.
Feederle R, Bannert H, Lips H, Müller-Lantzsch N, Delecluse HJ. The Epstein-Barr virus alkaline exonuclease BGLF5 serves pleiotropic functions in virus replication. J virol. 2009, 83:4952-62
Hutzinger R, Feederle R, Mrazek J, Schiefermeier N, Balwierz PJ, Zavolan M, Polacek N, Delecluse HJ, Hüttenhofer A. Expression and processing of a small nucleolar RNA from the Epstein-Barr virus genome. PLoS Pathog. 2009 Aug;5(8):e1000547.
Busse C, Feederle R, Schnölzer M, Behrends U, Mautner J, Delecluse HJ. Epstein-Barr viruses that express a CD21 antibody provide evidence that gp350's functions extend beyond B-cell surface binding. J Virol. 2010 84:1139-47
Feederle R, Linnstaedt SD, Bannert H, Lips H, Bencun M, Cullen BR, Delecluse HJ. A Viral microRNA cluster strongly potentiates the transforming properties of a Human Herpesvirus. PLoS Pathogens, 2011 PLoS Pathog 7(2): e1001294