Bone marrow stromal antigen 2

Definition:

IFN-induced antiviral host restriction factor which efficiently blocks the release of diverse mammalian enveloped viruses by directly tethering nascent virions to the membranes of infected cells. Acts as a direct physical tether, holding virions to the cell membrane and linking virions to each other. The tethered virions can be internalized by endocytosis and subsequently degraded or they can remain on the cell surface. In either case, their spread as cell-free virions is restricted. Its target viruses belong to diverse families, including retroviridae: human immunodeficiency virus type 1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), simian immunodeficiency viruses (SIVs), equine infectious anemia virus (EIAV), feline immunodeficiency virus (FIV), prototype foamy virus (PFV), Mason-Pfizer monkey virus (MPMV), human T-cell leukemia virus type 1 (HTLV-1), Rous sarcoma virus (RSV) and murine leukemia virus (MLV), flavivirideae: hepatitis C virus (HCV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), arenaviridae: lassa virus (LASV) and machupo virus (MACV), herpesviridae: kaposis sarcoma-associated herpesvirus (KSHV), rhabdoviridae: vesicular stomatitis virus (VSV), orthomyxoviridae: influenza A virus, paramyxoviridae: nipah virus, and coronaviridae: SARS-CoV. Can inhibit cell surface proteolytic activity of MMP14 causing decreased activation of MMP15 which results in inhibition of cell growth and migration. Can stimulate signaling by LILRA4/ILT7 and consequently provide negative feedback to the production of IFN by plasmacytoid dendritic cells in response to viral infection. Plays a role in the organization of the subapical actin cytoskeleton in polarized epithelial cells. Isoform 1 and isoform 2 are both effective viral restriction factors but have differing antiviral and signaling activities. Isoform 2 is resistant to HIV-1 Vpu-mediated degradation and restricts HIV-1 viral budding in the presence of Vpu. Isoform 1 acts as an activator of NF-kappa-B and this activity is inhibited by isoform 2.

References:

[1]. Fengwen Xu, et al. Tetherin inhibits prototypic foamy virus release. Virol J. 2011 May 2;8:198. [Content Brief]

[2]. Stuart J D Neil, et al. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature. 2008 Jan 24;451(7177):425-30. [Content Brief]

[3]. David Perez-Caballero, et al. Tetherin inhibits HIV-1 release by directly tethering virions to cells. Cell. 2009 Oct 30;139(3):499-511. [Content Brief]

[4]. Sheli R Radoshitzky, et al. Infectious Lassa virus, but not filoviruses, is restricted by BST-2/tetherin. J Virol. 2010 Oct;84(20):10569-80. [Content Brief]

[5]. Nolwenn Jouvenet, et al. Broad-spectrum inhibition of retroviral and filoviral particle release by tetherin. J Virol. 2009 Feb;83(4):1837-44. [Content Brief]

[6]. Andreas Hinz, et al. Structural basis of HIV-1 tethering to membranes by the BST-2/tetherin ectodomain. Cell Host Microbe. 2010 Apr 22;7(4):314-323. [Content Brief]

[7]. Avis Dafa-Berger, et al. Modulation of hepatitis C virus release by the interferon-induced protein BST-2/tetherin. Virology. 2012 Jul 5;428(2):98-111. [Content Brief]

[8]. Wei Cao, et al. Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction. J Exp Med. 2009 Jul 6;206(7):1603-14. [Content Brief]

[9]. Haitao Yang, et al. Structural insight into the mechanisms of enveloped virus tethering by tetherin. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18428-32. [Content Brief]

[10]. Gongping Gu, et al. BST-2 binding with cellular MT1-MMP blocks cell growth and migration via decreasing MMP2 activity. J Cell Biochem. 2012 Mar;113(3):1013-21. [Content Brief]

[11]. Rie Watanabe, et al. Influenza virus is not restricted by tetherin whereas influenza VLP production is restricted by tetherin. Virology. 2011 Aug 15;417(1):50-6. [Content Brief]

[12]. Luis J Cocka, et al. Identification of alternatively translated Tetherin isoforms with differing antiviral and signaling activities. PLoS Pathog. 2012 Sep;8(9):e1002931. [Content Brief]

[13]. Rachel L Kaletsky, et al. Tetherin-mediated restriction of filovirus budding is antagonized by the Ebola glycoprotein. Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2886-91. [Content Brief]

[14]. Shiu-Mei Wang, et al. Severe acute respiratory syndrome coronavirus spike protein counteracts BST2-mediated restriction of virus-like particle release. J Med Virol. 2019 Oct;91(10):1743-1750. [Content Brief]

[15]. Mariana G Bego, et al. Vpu Exploits the Cross-Talk between BST2 and the ILT7 Receptor to Suppress Anti-HIV-1 Responses by Plasmacytoid Dendritic Cells. PLoS Pathog. 2015 Jul 14;11(7):e1005024. [Content Brief]

[16]. Jessica M Weidner, et al. Interferon-induced cell membrane proteins, IFITM3 and tetherin, inhibit vesicular stomatitis virus infection via distinct mechanisms. J Virol. 2010 Dec;84(24):12646-57. [Content Brief]

[17]. Nanette Van Damme, et al. The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe. 2008 Apr 17;3(4):245-52. [Content Brief]

[18]. Claire Pardieu, et al. The RING-CH ligase K5 antagonizes restriction of KSHV and HIV-1 particle release by mediating ubiquitin-dependent endosomal degradation of tetherin. PLoS Pathog. 2010 Apr 15;6(4):e1000843. [Content Brief]

[19]. Justin K Taylor, et al. Severe Acute Respiratory Syndrome Coronavirus ORF7a Inhibits Bone Marrow Stromal Antigen 2 Virion Tethering through a Novel Mechanism of Glycosylation Interference. J Virol. 2015 Dec;89(23):11820-33. [Content Brief]

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