Kurzfassung

Tetraspanins are known as plasma membrane master organizers, which are relevant in infections with human papillomavirus (HPV), coronaviruses, influenza A virus, hepatitis C virus and human immunodeficiency virus. They act by defining on the cell surface sites for viral entry.

In the first funding period, we discovered that in HPV infection these sites contain two different tetraspanins (CD151 and CD63), the viral binding receptor integrin a6, integrin a3 for endocytosis, the protease ADAM17...Tetraspanins are known as plasma membrane master organizers, which are relevant in infections with human papillomavirus (HPV), coronaviruses, influenza A virus, hepatitis C virus and human immunodeficiency virus. They act by defining on the cell surface sites for viral entry.
 
In the first funding period, we discovered that in HPV infection these sites contain two different tetraspanins (CD151 and CD63), the viral binding receptor integrin a6, integrin a3 for endocytosis, the protease ADAM17 for signalling, and cytoskeletal components. We further found out, that the expression level of tetraspanins is associated with the susceptibility for infection, and that tetraspanin peptides block infection. Altogether, these data suggest that HPV uses a tetraspanin-based viral entry platform that has a defined architecture, and that tetraspanin peptides block infection, possibly by interfering with the formation of the platform. Because tetraspanins are involved in many viral infections (see above), tetraspanin blocking-peptides presumably ensure a wide range of uses.
 
In the next funding period, we aim for a deeper understanding of the platform and study the effect of peptide inhibition. First, we will study the state of tetraspanins in the moment of virus binding and briefly before membrane fission, and the influence of the tetraspanin level on platform formation and infection. Second, we will study what other components are in the platform with a focus on signalling molecules, in particular the tyrosine kinase ErbB2 that we found to be enriched in viral endosomes. Third, we will study whether ligands that promote infection, and peptides that block infection, interfere with stages of platform formation.
 
In conclusion, the viral entry platform plays a key role in the early steps of infection. Its understanding is not only interesting in the context of basic research, but opens an avenue for the development of broad-spectrum antiviral drugs.» weiterlesen» einklappen