Project Details
Projekt
Valency and Geometry of multivalent Glycolipid binding as cellular targeting mechnaism in viral infection
Applicant
Professor Dr. Helge Ewers
Subject Area
Virology
Term
from 2019 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 269564371
Glycolipid-binding viruses such as the DNA tumorvirus SV40 use clathrin-independent uptake pathways to enter cells for productive infection. To do so, they exploit the multivalent binding of SV40 to the glycolipid GM1 for membrane deformation leading to endocytosis. However, the physicochemical mechanism behind this pathway remains poorly understood and it is unclear, whether all glycolipid-binding polyomaviridae follow a similar route. At the same time, it remains unclear, why the globular GM1-binding SV40 virion is trafficked to the endoplasmatic reticulum (ER) leading to productive infection, while the likewise GM1-clustering Cholera toxin beta subunit (CTxB) ends up in the Golgi apparatus and unclustered GM1 molecules recycle to the plasma membrane. We aim here to find out, whether the globular geometric arrangement of viral ligands to carbohydrate binding sites is a general mechanism for membrane deformation in viral infection and how the number, nature and arrangement of carbohydrate binding sites controls cellular uptake and infection of virions. To do so, we will combine a number of live-cell, in situ and in vitro assays with high resolution and X-ray microscopy.
DFG Programme
Research Units
