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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 language | English |
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Article number | 32337 |
Number of pages | 18 |
Journal | Scientific Reports |
Volume | 6 |
Issue number | 1 |
Early online date | 31 Aug 2016 |
DOIs | |
Publication status | Published - Oct 2016 |
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Molecular Basis for the Trafficking of Transmembrane Proteins Through Ubiquitin, Syntenin-1 and Tollip Complexes
Berditchevski, F., Sundaresan, R. & Overduin, M.
Biotechnology & Biological Sciences Research Council
30/11/13 → 29/11/16
Project: Research Councils