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Novel Trafficking Pathway Controling HPV Infection

Laufzeit: 01.01.2015 - 31.12.2018

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Kurzfassung


In all eukaryotic cells, the endocytic apparatus manages the careful sorting of cargoes and the intracellular delivery of plasma membrane receptors and their ligands such as viruses. Clathrin-, caveolin- and dynamin-dependent endocytosis are the most extensively characterized routes, but attention is increasingly being paid to novel endocytosis and trafficking pathways. One of these novel pathways depends on tetraspanin CD151 and is used by human papillomavirus type 16 (HPV16) for infection...In all eukaryotic cells, the endocytic apparatus manages the careful sorting of cargoes and the intracellular delivery of plasma membrane receptors and their ligands such as viruses. Clathrin-, caveolin- and dynamin-dependent endocytosis are the most extensively characterized routes, but attention is increasingly being paid to novel endocytosis and trafficking pathways. One of these novel pathways depends on tetraspanin CD151 and is used by human papillomavirus type 16 (HPV16) for infection of human cells. Intracellular trafficking of incoming HPV viruses resulting in capsid disassembly and uncoating of the viral DNA is still poorly understood. We observed colocalisation of internalized HPV with tetraspanin CD63 and its interaction partner syntenin-1. The CD63/syntenin-1 complex regulates various aspects of trafficking. Therefore, these cellular proteins are attractive candidates that might regulate the so far uncharacterized pathway of papillomavirus entry. The research program will focus on the following aims:
 
To define the role of CD63 and syntenin-1 in HPV16 intracellular trafficking
To investigate interaction of syntenin-1 and CD63 in relation to HPV16 infection
To examine the significance of syntenin-1 phosphorylation in HPV infection.
To examine CD63 and syntenin-1 peptides or antibodies on their potential to block infectivity by different papillomaviruses. 
This study will contribute to a more in depth understanding of the endosomal trafficking pathway that controls HPV infection. Thus, detailed understanding of this pathway may provide a solid basis for developing novel therapeutic antiviral strategies.
 
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