{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BST2, also known as tetherin, CD317 or HM1.24, is an interferon‐inducible transmembrane protein that plays a pivotal role in innate antiviral defense against diverse enveloped viruses. It acts directly at the plasma membrane by “tethering” nascent virions—physically retaining fully formed virus particles at the cell surface—and thereby inhibiting their release and subsequent spread."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition, BST2 is expressed on certain immune cells (such as plasmacytoid dendritic cells) and functions as a negative immunoregulatory molecule by binding to receptors like ILT7, which modulates type I interferon responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Furthermore, signaling motifs within its cytoplasmic tail enable BST2 to activate proinflammatory NF‐κB pathways independently of its virion‐tethering activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Because of its potent antiviral functions, several viruses have evolved accessory proteins to counteract BST2. For example, HIV-1 encodes Vpu, which directly interacts with BST2 via their transmembrane domains and induces its removal from the cell surface through lysosomal degradation and sequestration away from sites of virion assembly."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Other lentiviruses, such as SIV and HIV-2, use Nef or Env to downregulate BST2, and evolutionary analyses reveal that species-specific differences in BST2 structure—shaped by positive selection—contribute to differential sensitivities to these viral antagonists."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "13"}]}, {"type": "t", "text": " Overall, BST2 operates as a multifaceted antiviral effector: it not only physically restricts the release of enveloped viruses but also contributes to immune signaling, thereby underscoring its crucial role in the host’s antiviral arsenal.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stuart J D Neil, Trinity Zang, Paul D Bieniasz "}, {"type": "b", "children": [{"type": "t", "text": "Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature06553"}], "href": "https://doi.org/10.1038/nature06553"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18200009"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18200009"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "David Perez-Caballero, Trinity Zang, Alaleh Ebrahimi, et al. 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