The CD63-Syntenin-1 Complex Controls Post-Endocytic Trafficking of Oncogenic Human Papillomaviruses.
Sci Rep
; 6: 32337, 2016 08 31.
Article
in En
| MEDLINE
| ID: mdl-27578500
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Calcium-Binding Proteins
/
Uterine Cervical Neoplasms
/
Cell Cycle Proteins
/
Papillomavirus Infections
/
Syntenins
/
Endosomal Sorting Complexes Required for Transport
/
Tetraspanin 30
Limits:
Female
/
Humans
Language:
En
Journal:
Sci Rep
Year:
2016
Type:
Article
Affiliation country:
Germany