title: Overexpression of inactive tetherin delGPI mutant inhibits HIV-1 Vpu-mediated antagonism of endogenous tetherin.
abstract: Tetherin/BST-2/CD317 inhibits HIV-1 release from infected cells, but the viral Vpu protein efficiently antagonizes this antiviral activity through direct interaction between the transmembrane (TM) domains of each protein. Here, we demonstrated that overexpression of an inactive tetherin delGPI mutant, the TM domain of which could competitively block Vpu targeting of endogenous tetherin, potently inhibited HIV-1 release from human tetherin-positive cells in both transient and stable expression conditions. These results also suggest that heterologous dimerization occurred between the delGPI mutant and endogenous tetherin. These findings suggest that blocking the Vpu/tetherin interface may be a novel therapeutic approach against HIV-1 release.
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, Changchun, Jilin Province, People's Republic of China.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Lv
authors.forename: Jiawen
authors.initials: J
authors.lastname: Wang
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Zuo
authors.forename: Donglai
authors.initials: D
authors.lastname: Liu
authors.forename: Jingyao
authors.initials: J
authors.lastname: Zhang
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Wu
authors.forename: Haihong
authors.initials: H
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.forename: Xianghui
authors.initials: X
authors.lastname: Yu
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005240:Feasibility Studies; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015316:Genetic Therapy; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D057809:HEK293 Cells; D015658:HIV Infections / Q000628:therapy; D015497:HIV-1 / Q000378:metabolism* / Q000472:pathogenicity; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D050505:Mutant Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D015202:Protein Engineering; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D021381:Protein Transport; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D017384:Sequence Deletion; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D014771:Virion / Q000378:metabolism / Q000472:pathogenicity; D057074:Virus Release; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; D054298:Human Immunodeficiency Virus Proteins; D050505:Mutant Proteins; D011994:Recombinant Proteins; 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