title: Direct internalization of cell-surface BST-2/tetherin by the HIV-1 accessory protein Vpu.
abstract: The host transmembrane protein BST-2/tetherin is a powerful antiviral factor that blocks the production of enveloped viruses. The HIV-1 accessory protein Vpu inhibits the antiviral activity of BST-2; however, the degradation pathway by which Vpu downregulates BST-2 from the cell surface and the actual subcellular location where Vpu targets BST-2 for downregulation remain controversial. Whereas one study showed that Vpu acts on constitutively endocytosed BST-2, we recently reported that Vpu can internalize BST-2 from the cell surface. Because the evidence for this conclusion was derived from indirect results, we present direct evidence in this study using an antibody internalization assay with an endocytosis-defective mutant of BST-2. The internalization of the BST-2 protein into cells coexpressing wild-type Vpu was observed when the cells were preincubated with antibodies against BST-2 at 37 degrees C, but not at 4 degrees C, for 10 min. These results strongly support our previous finding that continuously expressed de novo BST-2 at the cell surface is internalized by functional Vpu protein.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Iwabu
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujita
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Sata
authors.forename: Kenzo
authors.initials: K
authors.lastname: Tokunaga
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