Pathogenesis of Virus-Associated Tumors

Division of Pathogenesis of Virus Associated Tumors

Prof. Dr. Dr. Henri-Jacques Delecluse

Primary squamous epithelial cells infected with a recombinant Epstein-Barr virus tagged with a GFP gene.
© dkfz.de

The Epstein-Barr virus (EBV) is etiologically linked with 2% of all malignant tumors 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 the first described v-snoRNA1 or the BHRF1 and BART microRNA cluster. We have recently identified highly pathogenic EBV strains in tumors of the nasopharynx and in gastric carcinomas. These strains induce a very strong spontaneous lytic replication in infected B cells and infect epithelial cells with high efficiency (Figure). We have also generated EBV mutants that could be potentially used as vaccines. Indeed, these mutants produce large amounts of viral DNA-free virus-like particles (VLPs) that could elicit a strong immune response, but have lost any pathogenic potential.

FUTURE OUTLOOK
Future projects aim at pursuing the characterization of the various EBV strains that are found worldwide in the healthy and diseased population, and to generate vaccines to protect against highly pathogenic EBV strains.

Contact

Prof. Dr. Dr. Henri-Jacques Delecluse
Pathogenesis of Virus Associated Tumors (F100)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 4870

Selected Publications

  • Yu X. et al. (2015). Antigen-armed antibodies targeting B lymphoma cells effectively activate antigen-specific CD4+ T cells. Blood, 125(10), 1601-1610.
  • 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.
  • Tsai M.H. et al. (2013). Spontaneous lytic replication and epitheliotropism define an Epstein-Barr virus strain found in carcinomas. Cell Rep, 5(2), 458-470.
  • 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
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