title: 2-thio-6-azauridine inhibits Vpu mediated BST-2 degradation.
abstract: BACKGROUND
  BST-2 is an interferon-induced host restriction factor that inhibits the release of diverse mammalian enveloped viruses from infected cells by physically trapping the newly formed virions onto the host cell surface. Human Immunodeficiency Virus-1 (HIV-1) encodes an accessory protein Vpu that antagonizes BST-2 by down-regulating BST-2 from the cell surface.
  
  
  RESULTS
  Using a cell-based ELISA screening system, we have discovered a lead compound, 2-thio-6-azauridine, that restores cell surface BST-2 level in the presence of Vpu. This compound has no effect on the expression of BST-2 and Vpu, but inhibits Vpu-mediated BST-2 down-regulation and exerts no effect on Vpu-induced down-regulation of CD4 or KSHV K5 protein induced BST-2 down-regulation. 2-thio-6-azauridine suppresses HIV-1 production in a BST-2-dependent manner. Further results indicate that 2-thio-6-azauridine does not interrupt the interaction of BST-2 with Vpu and β-TrCP2, but decreases BST-2 ubiquitination.
  
  
  CONCLUSIONS
  Our study demonstrates the feasibility of using small molecules to target Vpu function and sensitize wild type HIV-1 to BST-2-mediated host restriction.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. huanlezq44@gmail.com.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. mizeyun@126.com.|Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, China. mizeyun@126.com.
authors.forename: Zeyun
authors.initials: Z
authors.lastname: Mi
authors.affiliation: Beijing Ditan Hospital, Capital Medical University, Beijing, China. hyming@medmail.com.cn.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. maling26@163.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Ma
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. jiweiding1223@hotmail.com.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Ding
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. wj_qhd@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. tantan10@163.com.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. muyangcy@sina.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. zhou_jim@hotmail.com.
authors.forename: Jinming
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. guoafei@hotmail.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Guo
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. lixiaoyu@imb.pumc.edu.cn.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. shancen@imb.pumc.edu.cn.
authors.forename: Shan
authors.initials: S
authors.lastname: Cen
mesh_terms: D019380:Anti-HIV Agents / Q000302:isolation & purification / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism*; D001380:Azauridine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D058851:GPI-Linked Proteins / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development*; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism*; D006801:Humans; D013891:Thiouridine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D019380:Anti-HIV Agents; D015703:Antigens, CD; D001380:Azauridine; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D013891:Thiouridine; D054334:Viral Regulatory and Accessory Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins; C009456:2-thio-6-azauridine