The CD63-syntenin-1 complex controls post-endocytic trafficking of oncogenic human papillomaviruses

Research output: Contribution to journalArticlepeer-review


  • Linda Gräßel
  • Laura Aline Fast
  • Konstanze D. Scheffer
  • Fatima Boukhallouk
  • Gilles A. Spoden
  • Stefan Tenzer
  • Klaus Boller
  • Ruzica Bago
  • Luise Florin

Colleges, School and Institutes


Human papillomaviruses enter host cells via a clathrin-independent endocytic pathway involving tetraspanin proteins. However, post-endocytic trafficking required for virus capsid disassembly remains unclear. Here we demonstrate that the early trafficking pathway of internalised HPV particles involves tetraspanin CD63, syntenin-1 and ESCRT-associated adaptor protein ALIX. Following internalisation, viral particles are found in CD63-positive endosomes recruiting syntenin-1, a CD63-interacting adaptor protein. Electron microscopy and immunofluorescence experiments indicate that the CD63-syntenin-1 complex controls delivery of internalised viral particles to multivesicular endosomes. Accordingly, infectivity of high-risk HPV types 16, 18 and 31 as well as disassembly and post-uncoating processing of viral particles was markedly suppressed in CD63 or syntenin-1 depleted cells. Our analyses also present the syntenin-1 interacting protein ALIX as critical for HPV infection and CD63-syntenin-1-ALIX complex formation as a prerequisite for intracellular transport enabling viral capsid disassembly. Thus, our results identify the CD63-syntenin-1-ALIX complex as a key regulatory component in post-endocytic HPV trafficking.


Original languageEnglish
Article number32337
Number of pages18
JournalScientific Reports
Issue number1
Early online date31 Aug 2016
Publication statusPublished - Oct 2016