Affinage

BST2

Bone marrow stromal antigen 2 · UniProt Q10589

Length
180 aa
Mass
19.8 kDa
Annotated
2026-06-09
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BST2 (tetherin/CD317/HM1.24) is an interferon-inducible host restriction factor that physically retains fully formed enveloped virus particles at the cell surface, blocking their release (PMID:18200009). This activity derives from its unusual dual-membrane-anchor topology: an N-terminal transmembrane domain and a C-terminal GPI anchor that places the protein in cholesterol-rich lipid raft microdomains and at both the apical surface and a juxtanuclear compartment (PMID:12956872). The extracellular domain forms a parallel, disulfide-bonded coiled-coil homodimer, the functional state for antiviral tethering (PMID:20880831), and each dimer bridges virion and cell membranes (PMID:19837671); both the transmembrane domain and the GPI anchor are required for tethering (PMID:25912717). Restriction extends across diverse enveloped viruses including HIV-1 and murine leukemia virus (PMID:18200009), influenza A (PMID:28087685), coronaviruses that bud at intracellular membranes such as HCoV-229E (PMID:24418563) and SARS-CoV-2 (PMID:37818801), and BST2 likewise tethers non-viral surface structures including exosomes and post-cytokinetic midbody remnants in a GPI-anchor-dependent manner (PMID:27657169, PMID:33711249). The short N-terminal cytoplasmic tail couples BST2 to multiple cellular processes: a non-canonical Tyr-6/Tyr-8 motif drives clathrin/AP-2-dependent endocytosis through direct binding to the alpha-adaptin appendage domain (PMID:19359243), and the tail links lipid rafts to the apical actin cytoskeleton via RICH2, EBP50, and ezrin (PMID:19273615). Numerous viral antagonists overcome BST2 by distinct routes: HIV-1 Vpu engages BST2 through their mutual transmembrane domains and triggers beta-TrCP-linked lysosomal degradation, surface downregulation, TGN trapping, and AP-1-dependent exclusion from assembly sites (PMID:19837671, PMID:21610122, PMID:27170757), KSHV K5 ubiquitinates the cytoplasmic lysines (PMID:19605472), and SIV Nef and various Env proteins act in species-specific or sequestration-based modes (PMID:19436700, PMID:19864625). Beyond virion tethering, BST2 serves as a ligand for the ILT7 receptor on plasmacytoid dendritic cells, providing negative feedback on type I IFN production (PMID:19564354), and can route intracellular non-enveloped targets for degradation via MARCH8-mediated ubiquitination and NDP52/ATG5-dependent selective autophagy (PMID:31868081, PMID:37155854). In vivo, IFNγ-induced BST2 promotes E-selectin-dependent hematopoietic stem cell relocalization and activation (PMID:33357430).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2003 High

    Establishing BST2's unusual dual-anchor topology defined the structural basis for how a single protein could later be understood to bridge two membranes.

    Evidence Expression cloning, detergent-resistant membrane fractionation, and microscopy in polarized epithelial cells

    PMID:12956872

    Open questions at the time
    • Did not connect topology to any antiviral function
    • Functional consequence of dual anchoring not yet defined
  2. 2008 High

    Identifying BST2/tetherin as the factor that retains virions on infected cells and explains the Vpu requirement answered why HIV-1 needs Vpu for efficient release.

    Evidence Expression correlation, siRNA depletion, microscopy, and virus release assays for HIV-1 and MLV

    PMID:18200009

    Open questions at the time
    • Molecular mechanism of tethering (direct bridging vs indirect) not established
    • Structural state of the active protein unknown
  3. 2009 High

    Mapping the cytoplasmic tail endocytosis motif and the actin-linkage partners revealed how BST2 traffics and connects lipid rafts to the cytoskeleton.

    Evidence Tyrosine mutagenesis with alpha-adaptin appendage binding assays; reciprocal knockdown and Co-IP for RICH2/EBP50/ezrin in polarized cells

    PMID:19273615 PMID:19359243

    Open questions at the time
    • Relationship between endocytosis and antiviral tethering not resolved
    • Physiological role of actin linkage beyond epithelial morphology unclear
  4. 2009 High

    Demonstrating BST2 as the ILT7 ligand established a non-tethering, immunoregulatory function feeding back on IFN production.

    Evidence Ligand identification screen, direct purified-protein binding, and pDC cytokine/signaling assays

    PMID:19564354

    Open questions at the time
    • Structural basis of BST2-ILT7 engagement not defined
    • Relationship between tethering form and ILT7-binding form unaddressed
  5. 2009 High

    Defining how HIV-1 Vpu, KSHV K5, and SIV Nef antagonize BST2 revealed multiple convergent strategies (TM-domain engagement/lysosomal degradation, cytoplasmic-lysine ubiquitination, and species-specific surface downregulation).

    Evidence Co-IP, TM and cytoplasmic-domain mutagenesis, ubiquitination assays, beta-TrCP knockdown, domain-swap and trans-complementation with virus release readouts

    PMID:19436700 PMID:19605472 PMID:19837671 PMID:19864625

    Open questions at the time
    • Whether degradation or surface displacement is the dominant antagonism mechanism not yet settled
    • Host machinery executing degradation not fully identified
  6. 2010 High

    Crystal structures resolved the functional oligomeric state, showing the parallel disulfide-bonded coiled-coil dimer is the primary antiviral species.

    Evidence X-ray crystallography at 2.6 and 3.45 Å, hydrodynamic analysis, and L70D mutagenesis with antiviral assays

    PMID:20880831

    Open questions at the time
    • Structure of the full membrane-anchored bridging configuration not captured
    • How dimer geometry physically spans virion and cell membranes inferred, not visualized
  7. 2010 High

    Dissecting Vpu mechanism into surface downregulation, ubiquitination of S/T residues, TGN trapping, and virion-membrane enrichment clarified that surface depletion rather than total degradation is the central counteraction.

    Evidence Comprehensive cytoplasmic-domain mutagenesis, quantitative endocytosis/recycling and de novo expression assays, quantitative immunoelectron microscopy, and virus release assays

    PMID:20147389 PMID:20147395 PMID:20980512 PMID:21610122

    Open questions at the time
    • Relative contribution of each Vpu route in physiological infection unclear
    • Adaptor machinery for TGN trapping not fully defined at this stage
  8. 2010 High

    Studies at the virological synapse showed BST2 restriction extends beyond cell-free release to modulate cell-to-cell transmission, with context-dependent outcomes.

    Evidence Tetherin-positive/-negative co-culture, quantitative transfer assays, siRNA depletion, and synapse microscopy

    PMID:20585562 PMID:20861257

    Open questions at the time
    • Conditions determining whether BST2 restricts vs promotes cell-to-cell spread not fully resolved
    • Single-lab quantitative transmission systems
  9. 2011 High

    Identifying HRS/ESCRT involvement and BST2's role in macrophage virus-containing compartments connected BST2 trafficking to lysosomal sorting and intracellular virion retention.

    Evidence siRNA knockdown, Co-IP showing Vpu-BST2-HRS tripartite association, and macrophage release/transmission assays

    PMID:21304933 PMID:22980332

    Open questions at the time
    • Whether HRS acts constitutively or only under Vpu not fully separated
    • Mechanism of incomplete Vpu antagonism in macrophages unexplained
  10. 2016 High

    Establishing BST2 as the AP-1-dependent factor excluded from assembly sites and as an exosomal tether broadened its role to general membrane-budding cargo retention.

    Evidence Vpu mutant panel with AP-1 interference and super-resolution microscopy; CRISPR knockout with GPI-anchor-dependent exosome rescue

    PMID:27170757 PMID:27657169

    Open questions at the time
    • Whether exosome and virion tethering use identical molecular geometry untested
    • Physiological consequences of exosome retention unclear
  11. 2019 High

    Discovering MARCH8/NDP52-dependent autophagic targeting of an intracellular viral nucleocapsid extended BST2 function from membrane tethering to selective autophagy of non-enveloped targets.

    Evidence Co-IP, ubiquitination assays, MARCHF8/ATG5 knockdown, autophagy vs proteasome inhibitors, and ChIP for IRF1-BST2 promoter binding in PEDV infection

    PMID:31868081

    Open questions at the time
    • Generality of this autophagic mechanism to other intracellular targets unknown
    • How a GPI-anchored membrane protein engages a cytosolic nucleocapsid not fully resolved
  12. 2021 High

    Showing BST2 tethers post-cytokinetic midbody remnants to the cell surface revealed a cell-intrinsic, non-immune function in cytokinesis-derived structure retention.

    Evidence CRISPR knockout, live imaging, and quantification of midbody remnant distribution

    PMID:33711249

    Open questions at the time
    • Downstream physiological role of midbody remnant retention unknown
    • Whether tethering uses the same dimeric bridging geometry as virions untested
  13. 2023 High

    Defining an ATG5/LC3C-associated pathway that recognizes dimerized, phosphorylated virus-tethering BST2 linked BST2 directly to inflammatory signaling, a pathway subverted by Vpu.

    Evidence Co-IP with dimerization- and phosphorylation-defective mutants, confocal microscopy, and inflammatory signaling assays

    PMID:37155854

    Open questions at the time
    • How phosphorylation is regulated during tethering not defined
    • Connection between this pathway and canonical NF-kB signaling unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BST2's distinct functional states (tethering dimer, ILT7 ligand, actin-linked raft organizer, autophagy adaptor) are partitioned and regulated within a single cell remains unresolved.
  • No unified model linking topological/oligomeric state to choice of function
  • Regulation switching BST2 between immunoregulatory and restriction roles unknown
  • Structure of the membrane-anchored virion-bridging configuration not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0060090 molecular adaptor activity 3 GO:0008289 lipid binding 2 GO:0008092 cytoskeletal protein binding 1 GO:0048018 receptor ligand activity 1
Localization
GO:0005768 endosome 3 GO:0005886 plasma membrane 3 GO:0005794 Golgi apparatus 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9612973 Autophagy 2
Partners
ATG5EBP50EZRHGSILT7MARCH8NDP52RICH2

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 BST2/CD317/tetherin was identified as the protein responsible for retaining fully formed retrovirus particles on infected cell surfaces (tethering activity). CD317 expression correlated with and induced a Vpu requirement for HIV-1 and murine leukemia virus particle release; depletion of CD317 abolished this requirement. CD317 caused retention of virions on cell surfaces and in CD317-positive intracellular compartments after endocytosis. Vpu co-localized with CD317 and inhibited these effects. Gene expression analysis combined with siRNA depletion, fluorescence microscopy co-localization, virus release assays Nature High 18200009
2003 BST2/HM1.24 has an unusual dual-anchor topology with an N-terminal transmembrane domain and a C-terminal GPI anchor, placing it in cholesterol-rich lipid raft microdomains. It localizes to both the cell surface (predominantly apical in polarized cells) and a juxtanuclear intracellular compartment, and is efficiently internalized from the cell surface. Expression cloning, cell fractionation, detergent-resistant membrane (lipid raft) isolation, fluorescence microscopy, polarized epithelial cell studies Traffic (Copenhagen, Denmark) High 12956872
2009 BST2 is a ligand for the ILT7 receptor expressed on plasmacytoid dendritic cells (pDCs). BST2 directly binds purified ILT7 protein, initiates signaling via the ILT7-FcεRIγ complex, and strongly inhibits IFN and proinflammatory cytokine production by pDCs, providing a negative feedback mechanism for IFN responses. Ligand identification screen, direct binding assay with purified proteins, pDC stimulation assays, signaling analysis The Journal of experimental medicine High 19564354
2009 KSHV K5 (a MARCH ubiquitin ligase) ubiquitinates lysines in the short N-terminal cytoplasmic domain of BST2, leading to rapid proteasomal/lysosomal degradation of BST2 despite its GPI anchor. BST2 lacking cytosolic lysines was K5-resistant; ubiquitin depletion by proteasome inhibitors restored BST2 surface expression. K5-mediated BST2 downregulation enables KSHV particle release. Ubiquitination assays, mutational analysis, proteasome/lysosome inhibitor treatments, virus release assays, primary KSHV infection experiments Journal of virology High 19605472
2009 HIV-1 Vpu physically interacts with BST-2 through their mutual transmembrane domains and leads to lysosomal (not proteasomal) degradation of BST-2. Degradation is partially controlled by β-TrCP. The primary site of Vpu action is the plasma membrane, where Vpu targets and actively internalizes cell-surface BST-2. Each dimerized BST-2 molecule acts as a bridge between viral and cell membranes in the tethering mechanism. Co-immunoprecipitation, transmembrane domain mutagenesis, lysosomal/proteasomal inhibitor assays, internalization assays, β-TrCP knockdown The Journal of biological chemistry High 19837671
2009 BST2 is internalized from lipid rafts at the cell surface via clathrin-mediated endocytosis. A non-canonical tyrosine-based motif containing Tyr-6 and Tyr-8 in the N-terminal cytoplasmic tail is essential for endocytosis through direct interaction with the α-adaptin subunit (specifically its appendage domain) of the AP-2 clathrin adaptor complex, not the μ2 subunit. Endocytosis assays, mutagenesis of tyrosine residues, co-immunoprecipitation of cytoplasmic tail with α-adaptin appendage domain, rescue experiments with appendage domain overexpression The Journal of biological chemistry High 19359243
2009 CD317/tetherin interacts indirectly with the apical actin cytoskeleton via RICH2, EBP50, and ezrin in polarized epithelial cells. Knockdown of either CD317 or RICH2 results in the same phenotype: loss of the apical actin network and microvilli, increased basal actin bundles, and reduced cell height, without loss of tight junctions or polarity. CD317 thus provides a physical link between lipid rafts and the apical actin network. siRNA knockdown, immunofluorescence microscopy, co-immunoprecipitation, morphological analysis of polarized epithelial cells The Journal of cell biology High 19273615
2009 SIV Nef acts as a species-specific tetherin antagonist for rhesus macaque and sooty mangabey tetherin but not human tetherin. Nef downregulates cell-surface expression of rhesus tetherin. The species-specificity of Nef for rhesus tetherin maps to four amino acids in the cytoplasmic domain of tetherin that are absent from human tetherin. The species-specificity of Vpu for human tetherin maps to amino acid differences in the transmembrane domain. Gene deletion (nef-deleted SIVmac239), trans-complementation, surface tetherin downregulation assays, domain-swap mutagenesis, virus release assays PLoS pathogens High 19436700
2010 The extracellular domain of BST2 forms a parallel dimeric coiled coil over its C-terminal two-thirds under oxidized conditions. Under reducing conditions it forms a tetramer via an antiparallel four-helix bundle at the N-terminal region. A mutation (L70D) that disrupts the tetramer reduced antiviral activity only ~3-fold, suggesting the primary functional state is a parallel disulfide-bound coiled-coil dimer with flexibility toward the N-terminus. X-ray crystallography (2.6 Å and 3.45 Å resolution structures), hydrodynamic analyses, site-directed mutagenesis with functional antiviral assays Proceedings of the National Academy of Sciences of the United States of America High 20880831
2010 Vpu stimulates ubiquitination of BST-2 at serine-threonine residues (specifically a serine-threonine-serine sequence) in the cytoplasmic domain. Mutation of all potential ubiquitination sites including lysines, cysteines, serines, and threonines abrogated Vpu-mediated ubiquitination. The serine-threonine-serine sequence specifically mediates downregulation of BST-2 from the cell surface and relief of virion release restriction. Ubiquitination assays, systematic mutagenesis of cytoplasmic domain residues (K, C, S, T), virus release assays, surface downregulation assays Journal of virology High 20980512
2010 Both HIV-1 Vpu and HIV-2 Env redirect tetherin away from the cell surface and sequester it in a perinuclear compartment overlapping with TGN markers. Sequestration by Vpu and HIV-2 Env is independent of tetherin's normal endocytosis trafficking pathway. Vpu additionally promotes total cellular tetherin degradation, indicating it uses more than one mechanism to counteract tetherin. Fluorescence microscopy, surface expression assays, subcellular fractionation, Vpu and HIV-2 Env expression studies Retrovirology Medium 20529266
2010 HIV-1 Vpu antagonizes CD317/tetherin by blocking both anterograde (biosynthetic) transport of newly synthesized CD317 and recycling of internalized CD317 to the cell surface, while CD317 endocytosis kinetics remain unaffected. Vpu traps trafficking CD317 at the TGN. This TGN trapping requires the conserved diserine S52/S56 motif of Vpu but does not require β-TrCP recruitment. Quantitative antibody-based endocytosis and recycling assays, microinjection/microscopy-based kinetic de novo expression assay, Vpu mutant analysis, primaquine treatment mBio High 21610122
2011 The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2 downregulation and degradation. BST-2 undergoes constitutive ESCRT-dependent sorting for lysosomal degradation that is enhanced by Vpu. HRS co-precipitates with both Vpu and BST-2, suggesting a tripartite complex. HRS depletion increases cellular BST-2 levels and restricts virus release. siRNA knockdown, co-immunoprecipitation, virus release assays, lysosomal degradation assays PLoS pathogens High 21304933
2010 CD317/tetherin is enriched in the HIV-1 virion membrane and in viral buds compared to the plasma membrane (as determined by quantitative immunoelectron microscopy), independent of Vpu. During HIV-1 infection, CD317 largely relocates from the plasma membrane to endosomes, an effect partially counteracted by Vpu. Quantitative immunoelectron microscopy, double-label immunoelectron microscopy Journal of virology High 20147389
2010 Antagonism of CD317-mediated virion release restriction by Vpu correlates with surface downregulation of CD317, not with intracellular degradation. Vpu can efficiently antagonize virion tethering in the absence of total CD317 degradation, establishing surface downregulation as the central mechanism. Analysis of CD317 mutants with altered sorting/ubiquitination motifs, surface expression assays, virus release assays Journal of virology Medium 20147395
2011 Tetherin/BST-2 is essential for the formation of an intracellular virus-containing compartment (VCC) in HIV-infected macrophages. Tetherin localizes at the virus-VCC membrane interface and physically tethers virions in VCCs. Tetherin knockdown diminished and redistributed VCCs within macrophages and promoted HIV release and cell-cell transmission. Vpu did not fully overcome tetherin-mediated restriction in macrophages despite working at the plasma membrane. Confocal microscopy, siRNA knockdown, HIV release and transmission assays in primary macrophages, co-localization analysis Cell host & microbe High 22980332
2016 Tetherin acts as an exosomal tether, retaining exosomes on the cell surface. BST2 knockout caused a 4-fold reduction in plasma membrane-associated exosomes with increased exosomes in medium. This phenotype was rescued by wild-type tetherin but not tetherin lacking its GPI anchor, establishing that the GPI anchor is required for this function. CRISPR knockout, exosome quantification, rescue experiments with tetherin mutants lacking GPI anchor eLife High 27657169
2021 BST2/tetherin tethers post-cytokinetic midbody remnants (MBRs) to the cell surface. BST2 is enriched at the midbody during cytokinesis and localizes to MBR surfaces. BST2 knockout causes detachment of MBRs from the cell surface and their accumulation in extracellular medium. The localization of BST2 at the MBR membrane is both necessary and sufficient for MBR-cell surface interaction. CRISPR knockout, live imaging, immunofluorescence microscopy, quantification of MBR distribution Current biology : CB High 33711249
2016 HIV-1 Vpu antagonizes CD317/tetherin by excluding it from HIV-1 assembly sites at the plasma membrane via AP-1-dependent mechanism. This exclusion depends on Vpu motifs for interaction with both AP-1 and CD317, and requires functional AP-1. Impairing recycling or anterograde transport of CD317 alone is insufficient for antagonism. A tripartite complex between Vpu, AP-1, and CD317 mediates displacement from assembly sites. Panel of Vpu mutants with specific interaction motif mutations, super-resolution microscopy, AP-1 knockdown/dominant-negative, co-immunoprecipitation, virus release assays Journal of virology High 27170757
2009 SIVtan Envelope glycoprotein can counteract tetherin from multiple primate species by intracellular sequestration of tetherin. SIVtan Env reduces surface tetherin levels and co-localizes with tetherin in intracellular tubulo-vesicular structures as shown by immuno-electron microscopy. Sensitivity to Vpu but not SIVtan Env can be transferred with the human tetherin transmembrane region. Virus release assays, surface tetherin quantification, immuno-electron microscopy, domain-swap mutagenesis with chimeric tetherin Proceedings of the National Academy of Sciences of the United States of America High 19864625
2019 BST2 restricts PEDV replication by binding the PEDV nucleocapsid (N) protein and targeting it for degradation via selective autophagy. BST2 recruits the E3 ubiquitin ligase MARCH8 to ubiquitinate the N protein; the ubiquitinated N protein is then recognized by NDP52 cargo receptor, which delivers it to autolysosomes. ATG5 knockdown or autophagy inhibitors (but not proteasome inhibitors) blocked N protein degradation. IRF1 induces BST2 expression by targeting its promoter during PEDV infection. Co-immunoprecipitation, siRNA knockdown of MARCHF8/ATG5, autophagy/proteasome inhibitors, ubiquitination assays, ChIP for IRF1-BST2 promoter interaction Autophagy High 31868081
2013 CD317/tetherin organizes membrane microdomains (lipid rafts). Knockdown of tetherin changes the distribution of lipid raft-localized proteins and alters lipid organization in the plasma membrane. These changes can be reversed by wild-type tetherin re-expression but not by any single domain deletion construct, indicating no individual feature of tetherin is dispensable for its lipid raft organizing function. siRNA knockdown, re-expression with domain deletion mutants, fluorescence microscopy, lipid raft fractionation Journal of cell science Medium 23378022
2013 BST2 co-localizes with HBV surface protein at multivesicular bodies (MVBs) and physically interacts with HBV particles, restricting HBV release. However, BST2-mediated HBV restriction is inactivated in hepatocytes through a novel mechanism requiring hepatocyte-specific cellular co-factors, and HBx exhibits enhanced interaction and co-localization with BST2 in hepatocytes. Co-immunoprecipitation, co-localization microscopy, HBV/HIV release assays in multiple cell types, siRNA knockdown Scientific reports Medium 26119070
2023 ATG5 recognizes cysteine-linked homodimerized BST2 and specifically engages phosphorylated BST2 that is tethering viruses at the plasma membrane. ATG5 and BST2 form a complex independently of Vpu and prior to LC3C recruitment in an LC3C-associated pathway. ATG12 conjugation to ATG5 is dispensable for this BST2 interaction. This LC3C-associated pathway is subverted by Vpu to attenuate inflammatory responses caused by virion retention. Co-immunoprecipitation, mutagenesis (dimerization-defective and phosphorylation-defective BST2 mutants), confocal microscopy, functional inflammatory signaling assays Proceedings of the National Academy of Sciences of the United States of America High 37155854
2013 BST-2/Tetherin facilitates HCMV entry into cells expressing high BST2 levels through a proposed reverse-tethering mechanism: BST2 present in HCMV virion envelopes interacts with BST2 in the target cell membrane, enhancing viral entry. BST2 was detected in HCMV particles, and siRNA knockdown of BST2 reduced HCMV infection. Virus recovery/entry assays, siRNA knockdown of BST2, virion fractionation showing BST2 in HCMV particles, THP-1 differentiation model PLoS pathogens Medium 22072961
2010 Tetherin accumulates with Gag at the contact zone between infected and target cells (virological synapse) but does not prevent virological synapse formation. In the presence of tetherin, viruses are transferred to target cells as abnormally large patches that accumulate at the target cell surface and have impaired fusion capacity, thereby reducing productive cell-to-cell transmission. Tetherin imprints virions in donor cells as a surface restriction mechanism. Tetherin-positive/-negative co-culture assays, fluorescence microscopy, flow cytometry-based quantitative transmission assays, siRNA depletion PLoS pathogens High 20585562
2020 IFNγ stimulation of hematopoietic stem cells (HSCs) increases expression of BST2, which is required for IFNγ-dependent HSC relocalization from the niche and activation. IFNγ stimulation increases E-selectin binding via BST2, and HSC homing to bone marrow depends on E-selectin binding. BST2-deficient HSCs remain more quiescent and resist depletion during chronic infection. Intravital 3D microscopy, BST2 knockout mice, E-selectin binding assays, chronic infection model, competitive transplantation Cell reports High 33357430
2019 CD317 activates EGFR in hepatocellular carcinoma cells by regulating EGFR's localization on the plasma membrane. CD317 associates with lipid rafts and releases EGFR from these ordered membrane domains, facilitating EGFR activation and downstream Ras-Raf-MEK-ERK and JAK-STAT signaling. CD317 knockdown reduces EGFR activation. siRNA/overexpression, lipid raft fractionation, co-localization microscopy, EGFR phosphorylation assays, xenograft models Cancer research Medium 30890618
2013 BST-2/Tetherin and CD4 can retro-translocate from the ER to the cytosol as partially folded and multimeric (dimeric, oxidized, disulfide-bonded) molecules. BST-2 is first exposed to the cytosol as a dimeric oxidized complex, which is then deglycosylated and reduced to monomers, suggesting that complete unfolding and cysteine reduction are not always required before ER-to-cytosol dislocation. Novel biotinylation technique in living cells for ER-to-cytosol retrotranslocation detection, proteasomal inhibition, biochemical analysis of disulfide bond status The Journal of biological chemistry Medium 24257748
2017 BST-2 restricts influenza A virus (IAV) release by tethering virus at the cell surface. However, the IAV M2 protein interacts with BST-2, reduces cell-surface BST-2 levels via the proteasomal pathway, and partially rescues IAV particle production. M2-deleted IAV is more restricted by BST-2 than wild-type IAV. Co-immunoprecipitation of M2 and BST-2, proteasomal inhibitor assays, virus-like particle assays, M2-deleted virus replication experiments The Biochemical journal Medium 28087685
2013 BST2 tethers HCoV-229E virions to cell surfaces or intracellular membranes even though HCoV-229E buds at the ER-Golgi intermediate compartment (ERGIC) rather than the plasma membrane. Electron microscopy directly visualized BST2 tethering virions at these intracellular compartments. BST2 knockdown enhanced HCoV-229E virion production. BST2 overexpression/knockdown with virus quantification, electron microscopy to visualize virion tethering Virology Medium 24418563
2009 BCA2/Rabring7 (RING-type E3 ubiquitin ligase) is a tetherin-interacting host protein that enhances tetherin-dependent restriction of HIV-1. In tetherin-positive cells, BCA2 facilitates internalization of HIV-1 virions into CD63+ intracellular vesicles leading to lysosomal degradation. BCA2 knockdown in HeLa cells reduced intracellular viral particle accumulation but virions remained on the plasma membrane. Co-immunoprecipitation, RNAi knockdown, virus release assays in tetherin-positive vs. tetherin-negative cells, fluorescence microscopy PLoS pathogens Medium 20019814
2013 Vpu expression causes loss of endogenous tetherin from lipid rafts and enhanced lysosomal degradation of tetherin. Internalised tetherin (in both control cells and Vpu-expressing cells) is found in non-raft fractions. Vpu intercepts newly internalised tetherin and diverts it for lysosomal degradation rather than recycling. No evidence was found for interaction between Vpu and endogenous tetherin at the cell surface. Lipid raft fractionation, confocal microscopy, lysosomal degradation assays, endocytosis tracking with endogenous (not overexpressed) tetherin PloS one Medium 24086611
2010 Tetherin enrichment at the virological synapse (VS) correlates with increased VS formation and accumulation of HIV envelope proteins on the cell surface in cells infected with Vpu-defective HIV-1. siRNA depletion of tetherin decreased VS formation and cell-to-cell transmission. Under some circumstances, tetherin can promote cell-to-cell transfer. Quantitative cell-to-cell transfer analysis, siRNA depletion, fluorescence microscopy of VS, type I interferon treatment experiments Journal of virology Medium 20861257
2015 Two tetherin isoforms differing in N-terminal length show distinct antiviral capabilities: the long isoform efficiently inhibited SFV (alphavirus) release while the short isoform did not, whereas both isoforms inhibited VSV exit. Both TM domain and GPI anchor are required for efficient anti-PFV tethering activity; dimerization and glycosylation are dispensable for anti-PFV activity. Isoform-specific expression assays, virus release assays with wild-type and mutant alphaviruses, tetherin domain deletion mutants Viruses Medium 25912717
2023 SARS-CoV-2 ORF3a reduces tetherin localisation within biosynthetic organelles (where coronaviruses bud) and increases tetherin localisation to late endocytic organelles by reducing retrograde recycling. SARS-CoV-2 Spike protein reduces total cellular tetherin levels. Tetherin depletion enhances SARS-CoV-2 viral titres, confirming it functions as a restriction factor for SARS-CoV-2. SARS-CoV-2 infection with tetherin knockdown, virus titer measurements, subcellular localization microscopy, individual viral protein expression studies EMBO reports Medium 37818801

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 1511 18200009
2003 Bst-2/HM1.24 is a raft-associated apical membrane protein with an unusual topology. Traffic (Copenhagen, Denmark) 370 12956872
2009 Species-specific activity of SIV Nef and HIV-1 Vpu in overcoming restriction by tetherin/BST2. PLoS pathogens 342 19436700
2009 Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction. The Journal of experimental medicine 258 19564354
2009 Molecular mechanism of BST2/tetherin downregulation by K5/MIR2 of Kaposi's sarcoma-associated herpesvirus. Journal of virology 227 19605472
2009 HIV-1 accessory protein Vpu internalizes cell-surface BST-2/tetherin through transmembrane interactions leading to lysosomes. The Journal of biological chemistry 204 19837671
2010 BST-2/tetherin: a new component of the innate immune response to enveloped viruses. Trends in microbiology 172 20688520
2010 Cell-cell spread of human immunodeficiency virus type 1 overcomes tetherin/BST-2-mediated restriction in T cells. Journal of virology 167 20861257
2010 HIV-1 Vpu and HIV-2 Env counteract BST-2/tetherin by sequestration in a perinuclear compartment. Retrovirology 144 20529266
2016 Tetherin is an exosomal tether. eLife 143 27657169
2009 Simian immunodeficiency virus envelope glycoprotein counteracts tetherin/BST-2/CD317 by intracellular sequestration. Proceedings of the National Academy of Sciences of the United States of America 143 19864625
2010 Tetherin restricts productive HIV-1 cell-to-cell transmission. PLoS pathogens 136 20585562
2019 BST2 suppresses porcine epidemic diarrhea virus replication by targeting and degrading virus nucleocapsid protein with selective autophagy. Autophagy 127 31868081
2009 HM1.24 is internalized from lipid rafts by clathrin-mediated endocytosis through interaction with alpha-adaptin. The Journal of biological chemistry 125 19359243
2010 Infectious Lassa virus, but not filoviruses, is restricted by BST-2/tetherin. Journal of virology 116 20686043
2010 Serine-threonine ubiquitination mediates downregulation of BST-2/tetherin and relief of restricted virion release by HIV-1 Vpu. Journal of virology 114 20980512
2009 A CD317/tetherin-RICH2 complex plays a critical role in the organization of the subapical actin cytoskeleton in polarized epithelial cells. The Journal of cell biology 112 19273615
2010 The great escape: viral strategies to counter BST-2/tetherin. PLoS pathogens 96 20485522
2013 BST-2/tetherin-mediated restriction of chikungunya (CHIKV) VLP budding is counteracted by CHIKV non-structural protein 1 (nsP1). Virology 92 23411007
2011 The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation. PLoS pathogens 91 21304933
2010 CD317/tetherin is enriched in the HIV-1 envelope and downregulated from the plasma membrane upon virus infection. Journal of virology 91 20147389
2013 The antiviral activities of tetherin. Current topics in microbiology and immunology 87 23686232
2010 Structural and functional studies on the extracellular domain of BST2/tetherin in reduced and oxidized conformations. Proceedings of the National Academy of Sciences of the United States of America 86 20880831
2010 Tetherin restricts direct cell-to-cell infection of HIV-1. Retrovirology 85 21184674
2011 HIV-1 Vpu blocks recycling and biosynthetic transport of the intrinsic immunity factor CD317/tetherin to overcome the virion release restriction. mBio 82 21610122
2009 Antiviral activity of the interferon-induced cellular protein BST-2/tetherin. AIDS research and human retroviruses 79 19929170
2009 BCA2/Rabring7 promotes tetherin-dependent HIV-1 restriction. PLoS pathogens 78 20019814
2012 Tetherin/BST-2 is essential for the formation of the intracellular virus-containing compartment in HIV-infected macrophages. Cell host & microbe 72 22980332
2014 Counteraction of the multifunctional restriction factor tetherin. Frontiers in microbiology 70 24782851
2010 Antagonism of CD317 restriction of human immunodeficiency virus type 1 (HIV-1) particle release and depletion of CD317 are separable activities of HIV-1 Vpu. Journal of virology 67 20147395
2015 The role of BST-2/Tetherin in host protection and disease manifestation. Immunity, inflammation and disease 66 27042298
2012 Influenza virus partially counteracts restriction imposed by tetherin/BST-2. The Journal of biological chemistry 66 22493439
2011 BST2/Tetherin enhances entry of human cytomegalovirus. PLoS pathogens 63 22072961
2012 BST-2/tetherin: structural biology, viral antagonism, and immunobiology of a potent host antiviral factor. Molecular immunology 58 23274150
2008 HM1.24 (CD317) is a novel target against lung cancer for immunotherapy using anti-HM1.24 antibody. Cancer immunology, immunotherapy : CII 58 18979097
2011 β-TrCP is dispensable for Vpu's ability to overcome the CD317/Tetherin-imposed restriction to HIV-1 release. Retrovirology 56 21310048
1999 Humanized anti-HM1.24 antibody mediates myeloma cell cytotoxicity that is enhanced by cytokine stimulation of effector cells. Blood 55 10339501
2006 Identification of a new HLA-A2-restricted T-cell epitope within HM1.24 as immunotherapy target for multiple myeloma. Experimental hematology 51 16569595
2012 Cutting edge: paradoxical roles of BST2/tetherin in promoting type I IFN response and viral infection. Journal of immunology (Baltimore, Md. : 1950) 49 22327075
2011 Upregulation of BST-2/Tetherin by HIV infection in vivo. Journal of virology 49 21849457
2020 Interferon Gamma Mediates Hematopoietic Stem Cell Activation and Niche Relocalization through BST2. Cell reports 47 33357430
2017 BST-2 Expression Modulates Small CD4-Mimetic Sensitization of HIV-1-Infected Cells to Antibody-Dependent Cellular Cytotoxicity. Journal of virology 45 28331088
2013 CD317/tetherin is an organiser of membrane microdomains. Journal of cell science 44 23378022
2023 BST2 induced macrophage M2 polarization to promote the progression of colorectal cancer. International journal of biological sciences 43 36594082
2011 Tetherin inhibits prototypic foamy virus release. Virology journal 43 21529378
2008 Interferon-alpha enhances CD317 expression and the antitumor activity of anti-CD317 monoclonal antibody in renal cell carcinoma xenograft models. Cancer science 43 19032371
2012 BST2/tetherin inhibits dengue virus release from human hepatoma cells. PloS one 42 23236425
2010 Endogenous CD317/Tetherin limits replication of HIV-1 and murine leukemia virus in rodent cells and is resistant to antagonists from primate viruses. Journal of virology 42 20702620
2018 BST2 promotes cell proliferation, migration and induces NF-κB activation in gastric cancer. Biotechnology letters 38 29774441
2013 BST2/CD317 counteracts human coronavirus 229E productive infection by tethering virions at the cell surface. Virology 38 24418563
2015 BST2/tetherin inhibition of alphavirus exit. Viruses 37 25912717
2010 HIV-1 Vpu targets cell surface markers CD4 and BST-2 through distinct mechanisms. Molecular aspects of medicine 37 20858517
2015 Identification of BST-2/tetherin-induced hepatitis B virus restriction and hepatocyte-specific BST-2 inactivation. Scientific reports 36 26119070
2011 Structural Basis for the Antiviral Activity of BST-2/Tetherin and Its Viral Antagonism. Frontiers in microbiology 35 22180752
2017 BST-2 restricts IAV release and is countered by the viral M2 protein. The Biochemical journal 33 28087685
2013 Ig-like transcript 7, but not bone marrow stromal cell antigen 2 (also known as HM1.24, tetherin, or CD317), modulates plasmacytoid dendritic cell function in primary human blood leukocytes. Journal of immunology (Baltimore, Md. : 1950) 33 23401591
2024 IFNα-induced BST2+ tumor-associated macrophages facilitate immunosuppression and tumor growth in pancreatic cancer by ERK-CXCL7 signaling. Cell reports 31 38602878
2018 BST-2 promotes survival in circulation and pulmonary metastatic seeding of breast cancer cells. Scientific reports 31 30514852
2019 CD317 Activates EGFR by Regulating Its Association with Lipid Rafts. Cancer research 30 30890618
2011 Tetherin and its viral antagonists. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 30 21222046
2016 Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection. Scientific reports 29 26846717
2016 HIV-1 Vpu Antagonizes CD317/Tetherin by Adaptor Protein-1-Mediated Exclusion from Virus Assembly Sites. Journal of virology 29 27170757
2010 BST-2 diminishes HIV-1 infectivity. Journal of virology 29 20861258
2019 Severe acute respiratory syndrome coronavirus spike protein counteracts BST2-mediated restriction of virus-like particle release. Journal of medical virology 28 31199522
2011 The expression of BST2 in human and experimental mouse brain tumors. Experimental and molecular pathology 28 21565182
2022 Multi-functional BST2/tetherin against HIV-1, other viruses and LINE-1. Frontiers in cellular and infection microbiology 27 36176574
2013 BST-2/tetherin is overexpressed in mammary gland and tumor tissues in MMTV-induced mammary cancer. Virology 27 23806386
2022 Unique Evolution of Antiviral Tetherin in Bats. Journal of virology 26 36173189
2014 Tetherin restricts HSV-2 release and is counteracted by multiple viral glycoproteins. Virology 26 25462350
2021 The viral restriction factor tetherin/BST2 tethers cytokinetic midbody remnants to the cell surface. Current biology : CB 25 33711249
2015 Bst2/Tetherin Is Induced in Neurons by Type I Interferon and Viral Infection but Is Dispensable for Protection against Neurotropic Viral Challenge. Journal of virology 25 26311886
2014 The novel immunotoxin HM1.24-ETA' induces apoptosis in multiple myeloma cells. Blood cancer journal 25 24927408
2016 Origins and Evolution of tetherin, an Orphan Antiviral Gene. Cell host & microbe 24 27427209
2012 Cell-cell transmission allows human T-lymphotropic virus 1 to circumvent tetherin restriction. Virology 24 23260108
2024 Spatial transcriptome profiling identifies DTX3L and BST2 as key biomarkers in esophageal squamous cell carcinoma tumorigenesis. Genome medicine 23 39696540
2023 Tetherin antagonism by SARS-CoV-2 ORF3a and spike protein enhances virus release. EMBO reports 23 37818801
2019 CRISPR-mediated activation of endogenous BST-2/tetherin expression inhibits wild-type HIV-1 production. Scientific reports 21 30816279
2015 Bone marrow stromal antigen 2 (BST-2) DNA is demethylated in breast tumors and breast cancer cells. PloS one 21 25860442
2013 CD4 and BST-2/tetherin proteins retro-translocate from endoplasmic reticulum to cytosol as partially folded and multimeric molecules. The Journal of biological chemistry 21 24257748
2023 BST2 regulated by the transcription factor STAT1 can promote metastasis, invasion and proliferation of oral squamous cell carcinoma via the AKT/ERK1/2 signaling pathway. International journal of oncology 20 36929425
2020 MicroRNA-760 inhibits cell viability and migration through down-regulating BST2 in gastric cancer. Journal of biochemistry 20 32167539
2013 Phosphatidylinositol 3-kinase is involved in Toll-like receptor 4-mediated BST-2/tetherin regulation. Cellular signalling 20 24036213
2012 HIV-1 Vpu's lipid raft association is dispensable for counteraction of the particle release restriction imposed by CD317/Tetherin. Virology 19 22222210
2021 CD11c+CD88+CD317+ myeloid cells are critical mediators of persistent CNS autoimmunity. Proceedings of the National Academy of Sciences of the United States of America 18 33785592
2012 β-TrCP dependency of HIV-1 Vpu-induced downregulation of CD4 and BST-2/tetherin. Current HIV research 18 22524179
2008 Chimeric and humanized anti-HM1.24 antibodies mediate antibody-dependent cellular cytotoxicity against lung cancer cells. Lung cancer (Amsterdam, Netherlands) 18 18524412
2023 ATG5 selectively engages virus-tethered BST2/tetherin in an LC3C-associated pathway. Proceedings of the National Academy of Sciences of the United States of America 17 37155854
2021 Zn-Induced Interactions Between SARS-CoV-2 orf7a and BST2/Tetherin. ChemistryOpen 17 34791819
2013 Combination with a defucosylated anti-HM1.24 monoclonal antibody plus lenalidomide induces marked ADCC against myeloma cells and their progenitors. PloS one 17 24386306
2023 Chimeric antigen receptor T cell-based targeting of CD317 as a novel immunotherapeutic strategy against glioblastoma. Neuro-oncology 16 37335916
2022 The Role of Long Noncoding RNA BST2-2 in the Innate Immune Response to Viral Infection. Journal of virology 16 35297670
2018 B49, a BST-2-based peptide, inhibits adhesion and growth of breast cancer cells. Scientific reports 16 29523843
2013 Antagonism to human BST-2/tetherin by Sendai virus glycoproteins. The Journal of general virology 16 23468424
2015 Human parainfluenza virus type 2 V protein inhibits and antagonizes tetherin. The Journal of general virology 15 26675672
2022 CD317-Positive Immune Stromal Cells in Human "Mesenchymal Stem Cell" Populations. Frontiers in immunology 14 35734183
2020 BST2 Promotes Tumor Growth via Multiple Pathways in Hepatocellular Carcinoma. Cancer investigation 14 32427495
2016 Tetherin/BST-2: Restriction Factor or Immunomodulator? Current HIV research 14 26957198
2015 CD317 is over-expressed in B-cell chronic lymphocytic leukemia, but not B-cell acute lymphoblastic leukemia. International journal of clinical and experimental pathology 14 25973046
2013 Expression of HIV-1 Vpu leads to loss of the viral restriction factor CD317/Tetherin from lipid rafts and its enhanced lysosomal degradation. PloS one 14 24086611
2011 The role of BST2/tetherin in feline retrovirus infection. Veterinary immunology and immunopathology 14 21715020

Missed literature

Know a paper Affinage missed for BST2? Flag it for the maintainers and the community.

No submissions yet.