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

摘要: 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 of internalised HPV particles involves CD63, syntenin-1 and ESCRT-associated adaptor protein ALIX. Following internalisation, viral are found in CD63-positive endosomes recruiting syntenin-1, CD63-interacting protein. Electron microscopy immunofluorescence experiments indicate CD63-syntenin-1 complex controls delivery to multivesicular endosomes. Accordingly, infectivity high-risk types 16, 18 31 as well post-uncoating processing was markedly suppressed CD63 or depleted cells. Our analyses also present interacting ALIX critical infection CD63-syntenin-1-ALIX formation prerequisite intracellular transport enabling disassembly. Thus, our results identify key regulatory component trafficking.