Up to 15% of all human cancers are caused by viruses, making it the second largest cancer risk; second only to smoking. The most common mode of tumor virus infection entails the inhibition of tumor suppressing proteins and related proteins. Recently, it has been shown that a set of DNA tumor causing viruses utilizes a completely unique strategy for infection. This mechanism (virocrine transformation) involves the ligand-independent activation of cellular growth pathways.

We are studying the structural basis of transformation of two viral proteins: E5 from the bovine papillomavirus, which activates the platelet-derived growth factor receptor and gp55p from the spleen focus forming virus, which activates the erythropoietin receptor. The envelope proteins of these viruses interact with the transmembrane domains of the receptors, forcing dimerization and activation. The interactions between viral protein monomers and receptor transmembrane domains are being studied by structural and computational methods.