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

Linda Gräßel, Laura Aline Fast, Konstanze D. Scheffer, Fatima Boukhallouk, Gilles A. Spoden, Stefan Tenzer, Klaus Boller, Ruzica Bago, Rajesh Sundaresan, Michael Overduin, Fedor Berditchevski, Luise Florin

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)
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Abstract

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
Volume6
Issue number1
Early online date31 Aug 2016
DOIs
Publication statusPublished - Oct 2016

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