P4 (Schelhaas)
The Functional Role of Glycosaminoglycan-Papillomavirus Interactions: Inhibition versus Activation
Human Papillomaviruses (HPVs) are a large family of transforming DNA viruses that cause asymptomatic infections, benign lesions, or anogential and oropharygeal cancers. In fact, at least 5% of human cancers are related to HPV infections. In a broad sense, one can distinguish between HPVs that specifically infect either the skin or the mucosa. However, it is unclear how this tissue tropism arises.
HPVs are thought to bind to sulfated polysaccharides for initial infection, in the case of HPV16 - the main cancer-causing type - to heparan sulfates. As sulfation patterns of these heparan sulfates vary in tissues, our main goal is to analyze the role(s) of heparan sulfate sulfation patterning for infection of diverse HPV types. Besides potentially explaining the tissue tropism of HPVs, the results of these studies will allow designing heparan sulfate mimetics as preventative viral measures for diverse HPV types. Collaborational interactions involve P1, P2, P3, P6, P7 and P8, where we will take advantage of the structural and synthetic methodology and expertise to address the structural prerequisites and consequences of HPV-ligand interactions, and where we will provide expertise for cell-based functional analyses.
