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Sci Rep. 2016 Aug 31;6:32337. doi: 10.1038/srep32337.

The CD63-Syntenin-1 Complex Controls Post-Endocytic Trafficking of Oncogenic Human Papillomaviruses.

Author information

1
Department of Medical Microbiology and Hygiene, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.
2
Department of Immunology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
3
Paul Ehrlich Institute, Langen, Germany.
4
School of Cancer Sciences and Department of Pathology, The University of Birmingham, Birmingham, United Kingdom.
5
Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.

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.

PMID:
27578500
PMCID:
PMC5006017
DOI:
10.1038/srep32337
[Indexed for MEDLINE]
Free PMC Article

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