{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T17:08:14Z","timestamp":1761844094019},"reference-count":39,"publisher":"American Society for Microbiology","issue":"19","license":[{"start":{"date-parts":[[2011,10,1]],"date-time":"2011-10-01T00:00:00Z","timestamp":1317427200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The interferon-inducible transmembrane protein BST-2 (CD317, tetherin) restricts the release of several enveloped viruses from infected cells. BST-2 is broadly active against retroviruses, including HIV-1 and HIV-2. To counteract this host defense, HIV-1 uses the accessory protein Vpu, whereas HIV-2 uses its envelope glycoprotein (Env). In both cases, viral antagonism is associated with decreased expression of BST-2 at the cell surface. Here, we provide evidence supporting a role for the clathrin-mediated endocytic pathway in the downregulation of BST-2 from the cell surface and the counteraction of restricted virion release. A catalytically inactive, dominant negative version of the vesicle \u201cpinch-ase\u201d dynamin 2 (dyn2K44A) inhibited the downregulation of BST-2 by Vpu, and it inhibited the release of wild-type (Vpu-expressing) HIV-1 virions. Similarly, dyn2K44A inhibited the downregulation of BST-2 by HIV-2 Env, and it inhibited the release of\n            <jats:italic>vpu<\/jats:italic>\n            -negative HIV-1 virions when HIV-2 Env was provided in\n            <jats:italic>trans<\/jats:italic>\n            . dyn2K44A inhibited Env more robustly than Vpu, suggesting that dynamin 2, while a cofactor for both Env and Vpu, might support just one of several pathways though which Vpu counteracts BST-2. In support of a role for clathrin in these effects, the C-terminal domain of the clathrin assembly protein AP180 also inhibited the downregulation of BST-2 by either Vpu or HIV-2 Env. Consistent with modulation of the postendocytic itinerary of BST-2, Vpu enhanced the accumulation of cell surface-derived BST-2 in transferrin-containing endosomes. Vpu also inhibited the transport of BST-2 from a brefeldin A-insensitive compartment to the cell surface, consistent with a block to endosomal recycling. We propose that HIV-1 Vpu, and probably HIV-2 Env, traps BST-2 in an endosomal compartment following endocytosis, reducing its level at the cell surface to counteract restricted viral release.\n          <\/jats:p>","DOI":"10.1128\/jvi.02633-10","type":"journal-article","created":{"date-parts":[[2011,8,4]],"date-time":"2011-08-04T14:04:47Z","timestamp":1312466687000},"page":"9834-9846","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":46,"title":["Role of the Endocytic Pathway in the Counteraction of BST-2 by Human Lentiviral Pathogens"],"prefix":"10.1128","volume":"85","author":[{"given":"David","family":"Lau","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093"}]},{"given":"Wilson","family":"Kwan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093"}]},{"given":"John","family":"Guatelli","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093"},{"name":"San Diego Veterans Affairs Healthcare System, San Diego, California 92161"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.6.3627-3638.2005"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02080-10"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.72.121801.161800"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00242-09"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000856"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000701"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.291.5506.1051"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.01.009"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02421-09"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-7-51"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.141.1.85"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.058305"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001265"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000429"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01515-09"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02636-09"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.135.2.341"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.118.2.267"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000450"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-09-243667"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020039"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06553"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1997.8839"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.08.039"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607622104"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb791"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.17.5008"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02978"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.003343"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00620-09"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2008.05.022"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00036-11"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2010.12.038"},{"key":"e_1_3_2_35_2","first-page":"551","article-title":"Serine-threonine ubiquitination mediates downregulation of BST-2\/tetherin and relief of restricted virion release by HIV-1 Vpu","volume":"85","author":"Tokarev A. A.","year":"2010","unstructured":"TokarevA. A. MunguiaJ. GuatelliJ. C. . 2010. Serine-threonine ubiquitination mediates downregulation of BST-2\/tetherin and relief of restricted virion release by HIV-1 Vpu. J. Virol. 85:551\u2013563.","journal-title":"J. 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