@article{e2252d63bda74a2ba6ec7e3df3dbbd89,
title = "BST-2 is rapidly down-regulated from the cell surface by the HIV-1 protein Vpu: Evidence for a post-ER mechanism of Vpu-action",
abstract = "Recent evidence suggests that transmembrane domain (TMD) interactions are essential for HIV-1 Vpu-mediated antagonism of the restriction factor BST-2/tetherin. We made Vpu TMD mutants to study the mechanism of BST-2 antagonism. Vpu-I17A, -A18F, -W22L, and -S23L co-localized with BST-2 within endosomal membranes while effectively enhancing virion release and down-regulating surface BST-2. However, Vpu-A18H was confined to an endoplasmic reticulum (ER)-like distribution, resulting in impaired down-regulation of BST-2 and reduced virion release. Brefeldin A confined wild type Vpu to the ER, resulting in a similarly impaired phenotype, as did the addition of a C-terminal ER-retention signal to Vpu. We determined the half-life of cell-surface BST-2 to be ~. 8. hours, whereas Vpu mediated an ~. 80% reduction of surface BST-2 within 6. hours, suggesting that TMD interactions between Vpu and BST-2 occur within post-ER membranes to directly and rapidly remove BST-2 from the cell surface and relieve restricted virion release.",
keywords = "BST-2, Brefeldin A, CD4, Endoplasmic reticulum, Tetherin, Vpu",
author = "Mark Skasko and Andrey Tokarev and Chen, {Cheng Chang} and Fischer, {Wolfgang B.} and Pillai, {Satish K.} and John Guatelli",
note = "Funding Information: We thank Jason Munguia and Marissa Suarez for technical assistance; Klaus Strebel for providing the proviral plasmid mutant of HIV-1NL4-3 vpuDEL-1 and the pcDNA3.1-based plasmid expressing codon optimized Vpu (pVphu); Jacek Skowronski for pCG-GFP; and Chugai Pharmaceuticals for the antibody to HM1.24/BST-2. Antibody to Vpu originated by Klaus Strebel was obtained from the National Institutes of Health AIDS Research & Reference Reagent Program. We thank Sherri Rostami, Deya Collier, and Nancy Keating for the p24 ELISAs; Neal Sekiya, Peggy O'Keefe, and Judy Nordberg for the flow cytometry; and Carol Ignacio and Parris Jordan for nucleotide sequencing. This work was supported by NIH Grant AI081668 to John Guatelli. Mark Skasko was supported by AIDS Training Grant T32AI007384 and an ARRA Supplement to NIH Grant AI081668 . WBF and CCC acknowledge National Yang-Ming University , the government of Taiwan and the National Science Council of Taiwan (NSC) for financial support.",
year = "2011",
month = mar,
day = "1",
doi = "10.1016/j.virol.2010.12.038",
language = "English",
volume = "411",
pages = "65--77",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
number = "1",
}
