Tetherin/BST-2 is an important host restriction factor that limits the replication of HIV and other enveloped viruses. Tetherin is a type II membrane glycoprotein with a very unusual domain structure that allows it to engage budding virions and retain them on the plasma membrane of infected cells. Following the initial report identifying tetherin as the host cell factor targeted by the HIV-1 Vpu gene, knowledge of the molecular, structural, and cellular biology of tetherin has rapidly advanced. This paper summarizes the discovery and impact of tetherin biology on the HIV field, with a focus on recent advances in understanding its structure and function. The relevance of tetherin to replication and spread of other retroviruses is also reviewed. Tetherin is a unique host restriction factor that is likely to continue to provide new insights into host-virus interactions and illustrates well the varied ways by which host organisms defend against viral pathogens. 1. Introduction Viruses and their host organisms engage in a series of conflicts in which viruses can be thought of as leading the offense, placing the host on defense. Host defenses against retroviral replication have arisen in a wide variety of forms. Classical cellular and humoral immune responses may limit retroviral replication and may be sufficient to prevent adverse outcomes in some host-virus interactions. However, throughout the evolution of mammals a series of alternative host defense factors have arisen whose apparent primary function is to counteract retroviruses in ways that lie outside of classical innate or adaptive immunity. These intrinsic host defense mechanisms against viruses have come to light largely through comparative studies of inhibition or “restriction” of replication of HIV or SIV in cells from different origins and are collectively referred to as host restriction factors. APOBEC3G, TRIM5alpha, and tetherin are the most prominent of a series of host restriction factors to be identified in recent years that limit HIV replication. This paper focuses on the discovery and subsequent characterization of tetherin, with an emphasis on recent work aimed at elucidating how its structure leads to retention of particles on the plasma membrane and on how Vpu acts to overcome tetherin-mediated restriction. 2. Identification of Tetherin as an Antiviral Host Restriction Factor The discovery of tetherin is intimately linked to studies of the effects of the HIV accessory gene Vpu. Vpu is a small integral membrane protein encoded by HIV-1 and a limited subset of SIV species. Early studies
References
[1]
K. Strebel, T. Klimkait, and M. A. Martin, “A novel gene of HIV-1, vpu, and its 16-kilodalton product,” Science, vol. 241, no. 4870, pp. 1221–1223, 1988.
[2]
E. F. Terwilliger, B. Godin, J. G. Sodroski, and W. A. Haseltine, “Construction and use of a replication-competent human immunodeficiency virus (HIV-1) that expresses the chloramphenicol acetyltransferase enzyme,” Proceedings of the National Academy of Sciences of the United States of America, vol. 86, no. 10, pp. 3857–3861, 1989.
[3]
T. Klimkait, K. Strebel, M. D. Hoggan, M. A. Martin, and J. M. Orenstein, “The human immunodeficiency virus type 1-specific protein vpu is required for efficient virus maturation and release,” Journal of Virology, vol. 64, no. 2, pp. 621–629, 1990.
[4]
R. L. Willey, A. Buckler-White, and K. Strebel, “Sequences present in the cytoplasmic domain of CD4 are necessary and sufficient to confer sensitivity to the human immunodeficiency virus type 1 Vpu protein,” Journal of Virology, vol. 68, no. 2, pp. 1207–1212, 1994.
[5]
M. E. Lenburg and N. R. Landau, “Vpu-induced degradation of CD4: requirement for specific amino acid residues in the cytoplasmic domain of CD4,” Journal of Virology, vol. 67, no. 12, pp. 7238–7245, 1993.
[6]
M. J. Vincent, N. U. Raja, and M. A. Jabbar, “Human immunodeficiency virus type 1 Vpu protein induces degradation of chimeric envelope glycoproteins bearing the cytoplasmic and anchor domains of CD4: role of the cytoplasmic domain in Vpu-induced degradation in the endoplasmic reticulum,” Journal of Virology, vol. 67, no. 9, pp. 5538–5549, 1993.
[7]
R. J. Geraghty and A. T. Panganiban, “Human immunodeficiency virus type 1 Vpu has a CD4- and an envelope glycoprotein-independent function,” Journal of Virology, vol. 67, no. 7, pp. 4190–4194, 1993.
[8]
M. Y. Chen, F. Maldarelli, M. K. Karczewski, R. L. Willey, and K. Strebel, “Human immunodeficiency virus type 1 Vpu protein induces degradation of CD4 in vitro: the cytoplasmic domain of CD4 contributes to Vpu sensitivity,” Journal of Virology, vol. 67, no. 7, pp. 3877–3884, 1993.
[9]
R. L. Willey, F. Maldarelli, M. A. Martin, and K. Strebel, “Human immunodeficiency virus type 1 Vpu protein induces rapid degradation of CD4,” Journal of Virology, vol. 66, no. 12, pp. 7193–7200, 1992.
[10]
F. Margottin, S. P. Bour, H. Durand et al., “A novel human WD protein, h-βTrCP, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif,” Molecular Cell, vol. 1, no. 4, pp. 565–574, 1998.
[11]
U. Schubert, L. C. Antón, I. Ba？ík et al., “CD4 glycoprotein degradation induced by human immunodeficiency virus type 1 Vpu protein requires the function of proteasomes and the ubiquitin- conjugating pathway,” Journal of Virology, vol. 72, no. 3, pp. 2280–2288, 1998.
[12]
M. Paul and M. A. Jabbar, “Phosphorylation of both phosphoacceptor sites in the HIV-1 Vpu cytoplasmic domain is essential for Vpu-mediated ER degradation of CD4,” Virology, vol. 232, no. 1, pp. 207–216, 1997.
[13]
S. Bour and K. Strebel, “The HIV-1 Vpu protein: a multifunctional enhancer of viral particle release,” Microbes and Infection, vol. 5, no. 11, pp. 1029–1039, 2003.
[14]
A. M. Sheehy, N. C. Gaddis, J. D. Choi, and M. H. Malim, “Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein,” Nature, vol. 418, no. 6898, pp. 646–650, 2002.
[15]
J. H. M. Simon, D. L. Miller, R. A. M. Fouchier, M. A. Soares, K. W. C. Peden, and M. H. Malim, “The regulation of primate immunodeficiency virus infectivity by Vif is cell species restricted: a role for Vif in determining virus host range and cross-species transmission,” The EMBO Journal, vol. 17, no. 5, pp. 1259–1267, 1998.
[16]
R. J. Geraghty, K. J. Talbot, M. Callahan, W. Harper, and A. T. Panganiban, “Cell type-dependence for Vpu function,” Journal of Medical Primatology, vol. 23, no. 2-3, pp. 146–150, 1994.
[17]
H. Sakai, K. Tokunaga, M. Kawamura, and A. Adachi, “Function of human immunodeficiency virus type 1 Vpu protein in various cell types,” Journal of General Virology, vol. 76, part 11, pp. 2717–2722, 1995.
[18]
V. Varthakavi, R. M. Smith, S. P. Bour, K. Strebel, and P. Spearman, “Viral protein U counteracts a human host cell restriction that inhibits HIV-1 particle production,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 25, pp. 15154–15159, 2003.
[19]
K. Hsu, J. Seharaseyon, P. Dong, S. Bour, and E. Marbán, “Mutual functional destruction of HIV-1 Vpu and host TASK-1 channel,” Molecular Cell, vol. 14, no. 2, pp. 259–267, 2004.
[20]
V. Varthakavi, E. Heimann-Nichols, R. M. Smith et al., “Identification of calcium-modulating cyclophilin ligand as a human host restriction to HIV-1 release overcome by Vpu,” Nature Medicine, vol. 14, no. 6, pp. 641–647, 2008.
[21]
S. J. Neil, S. W. Eastman, N. Jouvenet, and P. D. Bieniasz, “HIV-1 Vpu promotes release and prevents endocytosis of nascent retrovirus particles from the plasma membrane,” PLoS Pathogens, vol. 2, no. 5, article e39, 2006.
[22]
S. J. D. Neil, V. Sandrin, W. I. Sundquist, and P. D. Bieniasz, “An interferon-alpha-induced tethering mechanism inhibits HIV-1 and Ebola virus particle release but is counteracted by the HIV-1 Vpu protein,” Cell Host and Microbe, vol. 2, no. 3, pp. 193–203, 2007.
[23]
S. J. D. Neil, T. Zang, and P. D. Bieniasz, “Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu,” Nature, vol. 451, no. 7177, pp. 425–430, 2008.
[24]
J. Ishikawa, T. Kaisho, H. Tomizawa et al., “Molecular cloning and chromosomal mapping of a bone marrow stromal cell surface gene, BST2, that may be involved in pre-B-cell growth,” Genomics, vol. 26, no. 3, pp. 527–534, 1995.
[25]
T. Goto, S. J. Kennel, M. Abe et al., “A novel membrane antigen selectively expressed on terminally differentiated human B cells,” Blood, vol. 84, no. 6, pp. 1922–1930, 1994.
[26]
M. Vidal-Laliena, X. Romero, S. March, V. Requena, J. Petriz, and P. Engel, “Characterization of antibodies submitted to the B cell section of the 8th Human Leukocyte Differentiation Antigens Workshop by flow cytometry and immunohistochemistry,” Cellular Immunology, vol. 236, no. 1-2, pp. 6–16, 2005.
[27]
A. L. Blasius, E. Giurisato, M. Cella, R. D. Schreiber, A. S. Shaw, and M. Colonna, “Bone marrow stromal cell antigen 2 is a specific marker of type I IFN-producing cells in the naive mouse, but a promiscuous cell surface antigen following IFN stimulation,” Journal of Immunology, vol. 177, no. 5, pp. 3260–3265, 2006.
[28]
R. Rollason, V. Korolchuk, C. Hamilton, P. Schu, and G. Banting, “Clathrin-mediated endocytosis of a lipid-raft-associated protein is mediated through a dual tyrosine motif,” Journal of Cell Science, vol. 120, no. 21, pp. 3850–3858, 2007.
[29]
E. Bartee, A. McCormack, and K. Früh, “Quantitative membrane proteomics reveals new cellular targets of viral immune modulators,” PLoS Pathogens, vol. 2, no. 10, article e107, 2006.
[30]
N. Van Damme, D. Goff, C. Katsura 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 and Microbe, vol. 3, no. 4, pp. 245–252, 2008.
[31]
S. Kupzig, V. Korolchuk, R. Rollason, A. Sugden, A. Wilde, and G. Banting, “Bst-2/HM1.24 is a raft-associated apical membrane protein with an unusual topology,” Traffic, vol. 4, no. 10, pp. 694–709, 2003.
[32]
T. Ohtomo, Y. Sugamata, Y. Ozaki et al., “Molecular cloning and characterization of a surface antigen preferentially overexpressed on multiple myeloma cells,” Biochemical and Biophysical Research Communications, vol. 258, no. 3, pp. 583–591, 1999.
[33]
A. J. Andrew, E. Miyagi, S. Kao, and K. Strebel, “The formation of cysteine-linked dimers of BST-2/tetherin is important for inhibition of HIV-1 virus release but not for sensitivity to Vpu,” Retrovirology, vol. 6, article 80, 2009.
[34]
D. Perez-Caballero, T. Zang, A. Ebrahimi et al., “Tetherin inhibits HIV-1 release by directly tethering virions to cells,” Cell, vol. 139, no. 3, pp. 499–511, 2009.
[35]
A. Hinz, N. Miguet, G. Natrajan et al., “Structural basis of HIV-1 tethering to membranes by the BST-2/tetherin ectodomain,” Cell Host and Microbe, vol. 7, no. 4, pp. 314–323, 2010.
[36]
H. L. Schubert, Q. Zhai, V. Sandrin et al., “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, vol. 107, no. 42, pp. 17951–17956, 2010.
[37]
M. Swiecki, S. M. Scheaffer, M. Allaire, D. H. Fremont, M. Colonna, and T. J. Brett, “Structural and biophysical analysis of BST-2/tetherin ectodomains reveals an evolutionary conserved design to inhibit virus release,” The Journal of Biological Chemistry, vol. 286, no. 4, pp. 2987–2997, 2011.
[38]
H. Yang, J. Wang, X. Jia et al., “Structural insight into the mechanisms of enveloped virus tethering by tetherin,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 43, pp. 18428–18432, 2010.
[39]
K. Fitzpatrick, M. Skasko, T. J. Deerinck, J. Crum, M. H. Ellisman, and J. Guatelli, “Direct restriction of virus release and incorporation of the interferon-induced protein BST-2 into HIV-1 particles,” PLoS Pathogens, vol. 6, no. 3, Article ID e1000701, 2010.
[40]
J. Hammonds, J. J. Wang, H. Yi, and P. Spearman, “Immunoelectron microscopic evidence for tetherin/BST2 as the physical bridge between HIV-1 virions and the plasma membrane,” PLoS Pathogens, vol. 6, no. 2, Article ID e1000749, 2010.
[41]
A. J. Andrew, S. Kao, and K. Strebel, “C-terminal hydrophobic region in human bone marrow stromal cell antigen 2 (BST-2)/tetherin protein functions as second transmembrane motif,” The Journal of Biological Chemistry, vol. 286, no. 46, pp. 39967–39981, 2011.
[42]
A. Habermann, J. Krijnse-Locker, H. Oberwinkler et al., “CD317/tetherin is enriched in the HIV-1 envelope and downregulated from the plasma membrane upon virus infection,” Journal of Virology, vol. 84, no. 9, pp. 4646–4658, 2010.
[43]
J. Hammonds, L. Ding, H. Chu et al., “The tetherin/BST-2 coiled-coil ectodomain mediates plasma membrane microdomain localization and restriction of particle release,” Journal of Virology, vol. 86, no. 4, pp. 2259–2272, 2012.
[44]
M. Lehmann, S. Rocha, B. Mangeat et al., “Quantitative multicolor super-resolution microscopy reveals tetherin HIV-1 interaction,” PLoS Pathogens, vol. 7, no. 12, Article ID e1002456, 2011.
[45]
L. A. Lopez, S. J. Yang, C. M. Exline, S. Rengarajan, K. G. Haworth, and P. M. Cannon, “Anti-tetherin activities of HIV-1 Vpu and ebola virus glycoprotein do not involve removal of tetherin from lipid rafts,” Journal of Virology, vol. 86, no. 10, pp. 5467–5480, 2012.
[46]
J. V. Fritz, N. Tibroni, O. T. Keppler, and O. T. Fackler, “HIV-1 Vpu's lipid raft association is dispensable for counteraction of the particle release restriction imposed by CD317/Tetherin,” Virology, vol. 424, no. 1, pp. 33–44, 2012.
[47]
R. Rollason, V. Korolchuk, C. Hamilton, M. Jepson, and G. Banting, “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, vol. 184, no. 5, pp. 721–736, 2009.
[48]
Y. Katoh and M. Katoh, “Identification and characterization of ARHGAP27 gene in silico,” International Journal of Molecular Medicine, vol. 14, no. 5, pp. 943–947, 2004.
[49]
N. Richnau and P. Aspenstr？m, “Rich, a rho GTPase-activating protein domain-containing protein involved in signaling by Cdc42 and Rac1,” The Journal of Biological Chemistry, vol. 276, no. 37, pp. 35060–35070, 2001.
[50]
D. Reczek and A. Bretscher, “Identification of EPI64, a TBC/rabGAP domain-containing microvillar protein that binds to the first PDZ domain of EBP50 and E3KARP,” Journal of Cell Biology, vol. 153, no. 1, pp. 191–206, 2001.
[51]
Z. Songyang, S. E. Shoelson, M. Chaudhuri et al., “SH2 domains recognize specific phosphopeptide sequences,” Cell, vol. 72, no. 5, pp. 767–778, 1993.
[52]
M. W. McNatt, T. Zang, T. Hatziioannou et al., “Species-specific activity of HIV-1 Vpu and positive selection of tetherin transmembrane domain variants,” PLoS Pathogens, vol. 5, no. 2, Article ID e1000300, 2009.
[53]
L. Rong, J. Zhang, J. Lu et al., “The transmembrane domain of BST-2 determines its sensitivity to down-modulation by human immunodeficiency virus type 1 Vpu,” Journal of Virology, vol. 83, no. 15, pp. 7536–7546, 2009.
[54]
J. L. Douglas, K. Viswanathan, M. N. McCarroll, J. K. Gustin, K. Früh, and A. V. Moses, “Vpu directs the degradation of the human immunodeficiency virus restriction factor BST-2/tetherin via a βTrCP-dependent mechanism,” Journal of Virology, vol. 83, no. 16, pp. 7931–7947, 2009.
[55]
R. K. Gupta, S. Hué, T. Schaller, E. Verschoor, D. Pillay, and G. J. Towers, “Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion,” PLoS Pathogens, vol. 5, no. 5, Article ID e1000443, 2009.
[56]
B. Jia, R. Serra-Moreno, W. Neidermyer et al., “Species-specific activity of SIV Nef and HIV-1 Vpu in overcoming restriction by tetherin/BST2,” PLoS Pathogens, vol. 5, no. 5, Article ID e1000429, 2009.
[57]
M. Dubé, B. B. Roy, P. Guiot-Guillain et al., “Antagonism of tetherin restriction of HIV-1 release by Vpu involves binding and sequestration of the restriction factor in a perinuclear compartment,” PLoS Pathogens, vol. 6, no. 4, Article ID e1000856, 2010.
[58]
Y. Iwabu, H. Fujita, M. Kinomoto et al., “HIV-1 accessory protein Vpu internalizes cell-surface BST-2/tetherin through transmembrane interactions leading to lysosomes,” The Journal of Biological Chemistry, vol. 284, no. 50, pp. 35060–35072, 2009.
[59]
F. Zhang, S. J. Wilson, W. C. Landford et al., “Nef proteins from simian immunodeficiency viruses are tetherin antagonists,” Cell Host and Microbe, vol. 6, no. 1, pp. 54–67, 2009.
[60]
D. Sauter, M. Schindler, A. Specht et al., “Tetherin-driven adaptation of Vpu and Nef function and the evolution of pandemic and nonpandemic HIV-1 strains,” Cell Host and Microbe, vol. 6, no. 5, pp. 409–421, 2009.
[61]
R. K. Gupta and G. J. Towers, “A tail of Tetherin: how pandemic HIV-1 conquered the world,” Cell Host and Microbe, vol. 6, no. 5, pp. 393–395, 2009.
[62]
M. Shingai, T. Yoshida, M. A. Martin, and K. Strebel, “Some human immunodeficiency virus type 1 Vpu proteins are able to antagonize macaque BST-2 In Vitro and In vivo: Vpu-Negative simian-human immunodeficiency viruses are attenuated In vivo,” Journal of Virology, vol. 85, no. 19, pp. 9708–9715, 2011.
[63]
C. Goffinet, I. Allespach, S. Homann et al., “HIV-1 antagonism of CD317 is species specific and involves Vpu-mediated proteasomal degradation of the restriction factor,” Cell Host and Microbe, vol. 5, no. 3, pp. 285–297, 2009.
[64]
B. Mangeat, G. Gers-Huber, M. Lehmann, M. Zufferey, J. Luban, and V. Piguet, “HIV-1 Vpu neutralizes the antiviral factor tetherin/BST-2 by binding it and directing its beta-TrCP2-dependent degradation,” PLoS Pathogens, vol. 5, no. 9, Article ID e1000574, 2009.
[65]
F. Margottin, S. Benichou, H. Durand et al., “Interaction between the cytoplasmic domains of HIV-1 Vpu and CD4: role of Vpu residues involved in CD4 interaction and in vitro CD4 degradation,” Virology, vol. 223, no. 2, pp. 381–386, 1996.
[66]
C. Goffinet, S. Homann, I. Ambiel et al., “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, vol. 84, no. 8, pp. 4089–4094, 2010.
[67]
E. Miyagi, A. J. Andrew, S. Kao, and K. Strebe, “Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 8, pp. 2868–2873, 2009.
[68]
R. S. Mitchell, C. Katsura, M. A. Skasko et al., “Vpu antagonizes BST-2-mediated restriction of HIV-1 release via β-TrCP and endo-lysosomal trafficking,” PLoS Pathogens, vol. 5, no. 5, Article ID e1000450, 2009.
[69]
A. J. Andrew, E. Miyagi, and K. Strebel, “Differential effects of human immunodeficiency virus type 1 Vpu on the stability of BST-2/tetherin,” Journal of Virology, vol. 85, no. 6, pp. 2611–2619, 2011.
[70]
S. Bour, U. Schubert, K. Peden, and K. Strebel, “The envelope glycoprotein of human immunodeficiency virus type 2 enhances viral particle release: a Vpu-like factor?” Journal of Virology, vol. 70, no. 2, pp. 820–829, 1996.
[71]
S. Bour and K. Strebel, “The human immunodeficiency virus (HIV) type 2 envelope protein is a functional complement to HIV type 1 Vpu that enhances particle release of heterologous retroviruses,” Journal of Virology, vol. 70, no. 12, pp. 8285–8300, 1996.
[72]
G. D. Ritter, G. Yamshchikov, S. J. Cohen, and M. J. Mulligan, “Human immunodeficiency virus type 2 glycoprotein enhancement of particle budding: role of the cytoplasmic domain,” Journal of Virology, vol. 70, no. 4, pp. 2669–2673, 1996.
[73]
A. Le Tortorec and S. J. D. Neil, “Antagonism to and intracellular sequestration of human tetherin by the human immunodeficiency virus type 2 envelope glycoprotein,” Journal of Virology, vol. 83, no. 22, pp. 11966–11978, 2009.
[74]
P. Abada, B. Noble, and P. M. Cannon, “Functional domains within the human immunodeficiency virus type 2 envelope protein required to enhance virus production,” Journal of Virology, vol. 79, no. 6, pp. 3627–3638, 2005.
[75]
H. Hauser, L. A. Lopez, S. J. Yang et al., “HIV-1 Vpu and HIV-2 Env counteract BST-2/tetherin by sequestration in a perinuclear compartment,” Retrovirology, vol. 7, article 51, 2010.
[76]
B. Noble, P. Abada, J. Nunez-Iglesias, and P. M. Cannon, “Recruitment of the adaptor protein 2 complex by the human immunodeficiency virus type 2 envelope protein is necessary for high levels of virus release,” Journal of Virology, vol. 80, no. 6, pp. 2924–2932, 2006.
[77]
S. Bour, H. Akari, E. Miyagi, and K. Strebel, “Naturally occurring amino acid substitutions in the HIV-2 ROD envelope glycoprotein regulate its ability to augment viral particle release,” Virology, vol. 309, no. 1, pp. 85–98, 2003.
[78]
R. K. Gupta, P. Mlcochova, A. Pelchen-Matthews et al., “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, vol. 106, no. 49, pp. 20889–20894, 2009.
[79]
M. Mansouri, K. Viswanathan, J. L. Douglas et al., “Molecular mechanism of BST2/tetherin downregulation by K5/MIR2 of Kaposi's sarcoma-associated herpesvirus,” Journal of Virology, vol. 83, no. 19, pp. 9672–9681, 2009.
[80]
C. Pardieu, R. Vigan, S. J. Wilson 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 Pathogens, vol. 6, no. 4, Article ID e1000843, 2010.
[81]
P. Bates, R. L. Kaletsky, J. R. Francica, and C. Agrawal-Gamse, “Tetherin-mediated restriction of filovirus budding is antagonized by the Ebola glycoprotein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 8, pp. 2886–2891, 2009.
[82]
L. A. Lopez, S. J. Yang, H. Hauser et al., “Ebola virus glycoprotein counteracts BST-2/tetherin restriction in a sequence-independent manner that does not require tetherin surface removal,” Journal of Virology, vol. 84, no. 14, pp. 7243–7255, 2010.
[83]
A. Kühl, C. Banning, A. Marzi et al., “The Ebola virus glycoprotein and HIV-1 VPU employ different strategies to counteract the antiviral factor tetherin,” Journal of Infectious Diseases, vol. 204, supplement 3, pp. S850–S860, 2011.
[84]
N. Casartelli, M. Sourisseau, J. Feldmann et al., “Tetherin restricts productive HIV-1 cell-to-cell transmission,” PLoS Pathogens, vol. 6, no. 6, Article ID e1000955, 2010.
[85]
B. D. Kuhl, R. D. Sloan, D. A. Donahue, T. Bar-Magen, C. Liang, and M. A. Wainberg, “Tetherin restricts direct cell-to-cell infection of HIV-1,” Retrovirology, vol. 7, article 115, 2010.
[86]
C. Jolly, N. J. Booth, and S. J. D. Neil, “Cell-cell spread of human immunodeficiency virus type 1 overcomes tetherin/BST-2-mediated restriction in T cells,” Journal of Virology, vol. 84, no. 23, pp. 12185–12199, 2010.
[87]
C. M. Coleman, P. Spearman, and L. Wu, “Tetherin does not significantly restrict dendritic cell-mediated HIV-1 transmission and its expression is upregulated by newly synthesized HIV-1 Nef,” Retrovirology, vol. 8, article 26, 2011.
[88]
R. A. Liberatore and P. D. Bieniasz, “Tetherin is a key effector of the antiretroviral activity of type I interferon in vitro and in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 44, pp. 18097–18101, 2011.
[89]
B. S. Barrett, D. S. Smith, S. X. Li, K. Guo, K. J. Hasenkrug, and M. L. Santiago, “A single nucleotide polymorphism in tetherin promotes retrovirus restriction in vivo,” PLoS Pathogens, vol. 8, no. 3, Article ID e1002596, 2012.
[90]
M. Swiecki, Y. Wang, S. Gilfillan, D. J. Lenschow, and M. Colonna, “Cutting edge: paradoxical roles of BST2/tetherin in promoting type I IFN response and viral infection,” Journal of Immunology, vol. 188, no. 6, pp. 2488–2492, 2012.
