A rapid transfer of virions coated with heparan sulfate from the ECM to cell surface CD151 defines a step in the human papillomavirus infection cascade

Human Papillomaviruses (HPVs) are the underlying cause of several types of cancer though they are mostly known for their association with cervical carcinoma. Before establishing an infection, the virions must reach their target cells through a break in the epithelial barrier. After binding to heparan sulfate (HS) of the extracellular matrix (ECM), they translocate to the cell surface and co-internalize with the entry factor CD151.

For studying these early events of the infection cascade, we block the translocation from ECM-attachment sites to the cell body, release the block, and monitor the association of virions with CD151 or HS. We observe quick virion translocation from the ECM to the cell body within 15 min. During this process, virions associate with the tetraspanin CD151 present at the cell border or at filopodia. Translocating virions are decorated with HS, which they lose in the next few hours, presumably prior to endocytosis.

Our observations reveal a rapid step in the HPV infection cascade: the transfer of HS-coated virions from the ECM to CD151. This step is too fast to account for the asynchronous uptake of HPVs which is likely driven by glycan-processing and HS uncoating contributing to virus structural activation in preparation for endocytosis.