HIV-1 Antagonism of CD317 Is Species Specific and Involves Vpu-Mediated Proteasomal Degradation of the Restriction Factor

Goffinet, Christine; Allespach, Ina; Homann, Stefanie; Tervo, Hanna-Mari; Habermann, Anja; Rupp, Daniel; Oberbremer, Lena; Kern, Christian; Tibroni, Nadine; Welsch, Sonja; Krijnse‐Locker, Jacomine; Banting, George; Kräusslich, Hans‐Georg; Fackler, Oliver T.; Keppler, Oliver T.

doi:10.1016/j.chom.2009.01.009

Cited by 241 publications

(346 citation statements)

References 47 publications

(78 reference statements)

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“…4A; further images in Fig. S4), as has been previously described (1,9). On expression of SIVtan Env a striking re-localization of tetherin takes place and the tetherin and HIV-1 p17 signals separate ( Fig.…”

Section: Co-localization Between Tetherin and Mature Hiv-1 Gag At Thementioning

confidence: 65%

“…The mechanism of tetherin inhibition remains incompletely characterized but again, there are clearly significant mechanistic differences between the various viral antagonists. HIV-1 Vpu appears to lead to a reduction of steady-state tetherin levels (6,7,9) and exclusion from sites of particle assembly at the plasma membrane (2,26). Recent data suggest that Nef may remove tetherin from the cell surface (3) as it does other cell surface molecules (27).…”

Section: Discussionmentioning

confidence: 99%

“…S1). Mammalian tetherin sequences are divergent and this variability leads to species-specific sensitivity to tetherin antagonists (3,4,(7)(8)(9) (Figs. 1 and 2).…”

Section: Discussionmentioning

confidence: 99%

“…Several recent studies have suggested that Vpu expression leads to tetherin degradation (6,7,9). We therefore examined the impact of SIVtan envelope expression on tetherin levels.…”

Section: Sivtan Env Does Not Reduce Total Tetherin Levels But Depletesmentioning

confidence: 99%

“…It is proposed to form a protein tether linking assembled virions to infected cells, leading to their endocytosis and degradation in lysosomes (1,6). All tetherin variants tested thus far inhibit the release of enveloped viral particles including retroviruses, filoviruses, and arena viruses (1,2,(7)(8)(9)(10). Many simian immunodeficiency variants do not encode a Vpu protein, suggesting the existence of an alternative means of overcoming tetherin restriction.…”

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confidence: 99%

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Simian immunodeficiency virus envelope glycoprotein counteracts tetherin/BST-2/CD317 by intracellular sequestration

Mlčochová²,

Pelchen–Matthews³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

150

185

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Tetherin is an IFN-inducible restriction factor that inhibits HIV-1 particle release in the absence of the HIV-1 countermeasure, viral protein U (Vpu). Although ubiquitous in HIV-1 and simian immunodeficiency viruses from chimpanzees, greater spot nosed monkeys, mustached monkeys, and Mona monkeys, other primate lentiviruses do not encode a Vpu protein. Here we demonstrate that SIV from Tantalus monkeys (SIVtan) encodes an envelope glycoprotein (SIVtan Env) able to counteract tetherin from Tantalus monkeys, rhesus monkeys, sooty mangabeys, and humans, but not from pigs. We show that sensitivity to Vpu but not SIVtan Env can be transferred with the human tetherin transmembrane region. We also identify a mutation in the tetherin extracellular domain, which almost completely abolishes sensitivity of human tetherin to SIVtan Env without compromising antiviral activity or sensitivity to Vpu. SIVtan Env expression results in a reduction of surface tetherin, as well as reduction in tetherin co-localization with mature surface-associated virus. Immuno-electron microscopy reveals co-localization of SIVtan Env with tetherin in intracellular tubulo-vesicular structures, suggesting that tetherin is sequestered away from budding virions at the cell surface. Along with HIV-1 Vpu and SIV Nef, envelope glycoprotein is the third and most broadly active lentiviral-encoded tetherin countermeasure to be described. Our observations emphasize the importance of tetherin in protecting mammals against viral infection and suggest that HIV-1 Vpu inhibitors may select active envelope mutants.HIV ͉ restriction ͉ innate immunity

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Section: Co-localization Between Tetherin and Mature Hiv-1 Gag At Thementioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

“…S1). Mammalian tetherin sequences are divergent and this variability leads to species-specific sensitivity to tetherin antagonists (3,4,(7)(8)(9) (Figs. 1 and 2).…”

Section: Discussionmentioning

confidence: 99%

“…Several recent studies have suggested that Vpu expression leads to tetherin degradation (6,7,9). We therefore examined the impact of SIVtan envelope expression on tetherin levels.…”

Section: Sivtan Env Does Not Reduce Total Tetherin Levels But Depletesmentioning

confidence: 99%

mentioning

confidence: 99%

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Simian immunodeficiency virus envelope glycoprotein counteracts tetherin/BST-2/CD317 by intracellular sequestration

Mlčochová²,

Pelchen–Matthews³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

150

185

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Lymphocyte‐specific protein 1 (LSP1) regulates bone marrow stromal cell antigen 2 (BST‐2)‐mediated intracellular trafficking of HIV‐1 in dendritic cells

2020

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Human immunodeficiency virus type 1 (HIV‐1) subverts intracellular trafficking pathways to avoid its degradation and elimination, thereby enhancing its survival and spread. The molecular mechanisms involved in intracellular transport of HIV‐1 are not yet fully defined. We demonstrate that the actin‐binding protein lymphocyte‐specific protein 1 (LSP1) interacts with the interferon‐inducible protein bone marrow stromal antigen 2 (BST‐2) in dendritic cells (DCs) to facilitate both endocytosis of surface‐bound HIV‐1 and the formation of early endosomes. Analysis of the molecular interaction between LSP1 and BST‐2 reveals that the N terminus of LSP1 interacts with BST‐2. Overall, we identify a novel mechanism of intracellular trafficking of HIV‐1 in DCs centering on the LSP1/BST‐2 complex. We also show that the HIV‐1 accessory protein Vpu subverts this pathway by inducing proteasomal degradation of LSP1, augmenting cell–cell transmission of HIV‐1.

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The role of BST‐2/Tetherin in host protection and disease manifestation

Mahauad‐Fernandez

Okeoma

2015

Immunity, Inflammation and Disease

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Host cells respond to viral infections by activating immune response genes that are not only involved in inflammation, but may also predispose cells to cancerous transformation. One such gene is BST‐2, a type II transmembrane protein with a unique topology that endows it tethering and signaling potential. Through this ability to tether and signal, BST‐2 regulates host response to viral infection either by inhibiting release of nascent viral particles or in some models inhibiting viral dissemination. However, despite its antiviral functions, BST‐2 is involved in disease manifestation, a function linked to the ability of BST‐2 to promote cell‐to‐cell interaction. Therefore, modulating BST‐2 expression and/or activity has the potential to influence course of disease.

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HIV-1 Antagonism of CD317 Is Species Specific and Involves Vpu-Mediated Proteasomal Degradation of the Restriction Factor

Cited by 241 publications

References 47 publications

Simian immunodeficiency virus envelope glycoprotein counteracts tetherin/BST-2/CD317 by intracellular sequestration

Simian immunodeficiency virus envelope glycoprotein counteracts tetherin/BST-2/CD317 by intracellular sequestration

Lymphocyte‐specific protein 1 (LSP1) regulates bone marrow stromal cell antigen 2 (BST‐2)‐mediated intracellular trafficking of HIV‐1 in dendritic cells

The role of BST‐2/Tetherin in host protection and disease manifestation

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