EBV strains and cancer
Project leader:
The Epstein-Barr virus (EBV) chronically infects the large majority of the world population, usually without clinical consequences.
However, in a minority of individuals, EBV infection is associated with the development of a variety of diseases, ranging from infectious mononucleosis (IM) syndromes to various cancers.
Although the virus homogeneously targets populations from all geographic areas, the incidence of the diseases it causes can vary drastically.
Whilst IM is common in Western populations, Burkitt’s lymphoma (BL) is endemic in Equatorial Africa and nasopharyngeal carcinoma (NPC) is one of the most common tumors encountered in South-East Asia.
What causes these variations in disease incidence has been unclear for a long time, although the age at which EBV infection takes place, environmental factors such as food contaminations with nitrosamines and phorbol esters or smoking, and concurrent diseases such as malaria are all known to play an important role.
We have found that M81, a virus isolated from a Chinese patient with nasopharyngeal carcinoma (NPC), shows remarkable similarity to other NPC viruses, but was divergent from all other known strains.
M81 exhibited a reversed tropism relative to common strains, with a reduced ability to infect B-cells and a high propensity to infect epithelial cells, in agreement with its isolation from carcinomas.
M81 spontaneously replicated in B-cells in vitro and in vivo at unusually high levels, in line with the enhanced viral replication observed in NPC patients (see cartoon).
© dkfz.de
This means that there are EBV subtypes with enhanced pathogenic properties.
Current projects include the cloning and characterization of EBVs present in other carcinomas, such as gastric carcinoma, and in other hematopoietic tumors.
We also intend to understand the molecular basis of the phenotypic differences between the different EBV subtypes.