title: Epitope tags beside the N-terminal cytoplasmic tail of human BST-2 alter its intracellular trafficking and HIV-1 restriction.
abstract: BST-2 blocks the particle release of various enveloped viruses including HIV-1, and this antiviral activity is dependent on the topological arrangement of its four structural domains. Several functions of the cytoplasmic tail (CT) of BST-2 have been previously discussed, but the exact role of this domain remains to be clearly defined. In this study, we investigated the impact of truncation and commonly-used tags addition into the CT region of human BST-2 on its intracellular trafficking and signaling as well as its anti-HIV-1 function. The CT-truncated BST-2 exhibited potent inhibition on Vpu-defective HIV-1 and even wild-type HIV-1. However, the N-terminal HA-tagged CT-truncated BST-2 retained little antiviral activity and dramatically differed from its original protein in the cell surface level and intracellular localization. Further, we showed that the replacement of the CT domain with a hydrophobic tag altered BST-2 function possibly by preventing its normal vesicular trafficking. Notably, we demonstrated that a positive charged motif "KRXK" in the conjunctive region between the cytotail and the transmembrane domain which is conserved in primate BST-2 is important for the protein trafficking and the antiviral function. These results suggest that although the CT of BST-2 is not essential for its antiviral activity, the composition of residues in this region may play important roles in its normal trafficking which subsequently affected its function. These observations provide additional implications for the structure-function model of BST-2.
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Lv
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, P.R. China; Center for New Medicine Research, Changchun University of Chinese Medicine, Changchun, P.R. China.
authors.forename: Jiawen
authors.initials: J
authors.lastname: Wang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Jingyao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Biao
authors.initials: B
authors.lastname: Zhang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Wang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zuo
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Donglai
authors.initials: D
authors.lastname: Liu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Li
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Wu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Xinghong
authors.initials: X
authors.lastname: Zhao
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, P.R. China.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Yu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D000939:Epitopes / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000737:chemistry / Q000378:metabolism; D057809:HEK293 Cells; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D000939:Epitopes; D058851:GPI-Linked Proteins; D021382:Protein Sorting Signals; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2