Topic
Tetherin
About: Tetherin is a research topic. Over the lifetime, 565 publications have been published within this topic receiving 30837 citations. The topic is also known as: bone marrow stromal antigen 2 & BST2.
Papers published on a yearly basis
Papers
TL;DR: CD317 (also called BST2 or HM1), a membrane protein of previously unknown function, is identified as a tetherin andhibition of Vpu function and consequent mobilization of tetherin’s antiviral activity is a potential therapeutic strategy in HIV/AIDS.
Abstract: Human cells possess an antiviral activity that inhibits the release of retrovirus particles, and other enveloped virus particles, and is antagonized by the HIV-1 accessory protein, Vpu. This antiviral activity can be constitutively expressed or induced by interferon-α, and it consists of protein-based tethers, which we term ‘tetherins’, that cause retention of fully formed virions on infected cell surfaces. Using deductive constraints and gene expression analyses, we identify CD317 (also called BST2 or HM1.24), a membrane protein of previously unknown function, as a tetherin. Specifically, CD317 expression correlated with, and induced, a requirement for Vpu during HIV-1 and murine leukaemia virus particle release. Furthermore, in cells where HIV-1 virion release requires Vpu expression, depletion of CD317 abolished this requirement. CD317 caused retention of virions on cell surfaces and, after endocytosis, in CD317-positive compartments. Vpu co-localized with CD317 and inhibited these effects. Inhibition of Vpu function and consequent mobilization of tetherin’s antiviral activity is a potential therapeutic strategy in HIV/AIDS. Studies of Vpu, an HIV-1 accessory protein required for efficient HIV-1 particle release in some human cells, pointed to the existence of a tether based in a cell surface protein inducible by interferon-α. That tether has now been identified as the host cell molecule CD317— renamed tetherin — a membrane protein with no previously known function. Tetherin is shown to be involved in the retention of HIV-1 virions at the cell surface. Vpu neutralizes its effect, allowing the release and propagation of virus particles. Inhibition of Vpu function is therefore a possible therapeutic strategy in HIV/AIDS. The HIV protein Vpu is required for the release of viral particles. This paper shows that it counteracts the host cell protein CD317, renamed as tetherin. Tetherin is involved in the retention of newly budded HIV-1 virions at the cell surface.
1,881 citations
TL;DR: The unusual structure of BST-2, which includes a transmembrane domain and a lumenal GPI anchor, may allow it to retain nascent enveloped virions on cellular membranes, providing a mechanism of viral restriction counteracted by a specific viral accessory protein.
1,105 citations
TL;DR: Recent advances in understanding the interactions of the HIV-1 Nef, Vif, Vpu, and Vpr proteins with factors and pathways expressed in cells of the immune system are discussed.
635 citations
TL;DR: It is demonstrated, through mutational analyses and domain replacement experiments, that tetherin configuration rather than primary sequence is critical for antiviral activity and that infiltration of virion envelopes by one or both of tetherin's membrane anchors is necessary to tether enveloped virus particles that bud through the plasma membrane.
622 citations
TL;DR: It is demonstrated that the presence of the HIV-1-encoded integral membrane protein Vpu can reduce the formation of Env-CD4 complexes, resulting in increased gp160 processing and decreased CD4 stability.
Abstract: CD4 is an integral membrane glycoprotein which is known as the human immunodeficiency virus (HIV) receptor for infection of human cells. The protein is synthesized in the endoplasmic reticulum (ER) and subsequently transported to the cell surface via the Golgi complex. HIV infection of CD4+ cells leads to downmodulation of cell surface CD4, due at least in part to the formation of stable intracellular complexes between CD4 and the HIV type 1 (HIV-1) Env precursor polyprotein gp160. This process "traps" both proteins in the ER, leading to reduced surface expression of CD4 and reduced processing of gp160 to gp120 and gp41. We have recently demonstrated that the presence of the HIV-1-encoded integral membrane protein Vpu can reduce the formation of Env-CD4 complexes, resulting in increased gp160 processing and decreased CD4 stability. We have studied the effect of Vpu on CD4 stability and found that Vpu induces rapid degradation of CD4, reducing the half-life of CD4 from 6 h to 12 min. By using a CD4-binding mutant of gp160, we were able to show that this Vpu-induced degradation of CD4 requires retention of CD4 in the ER, which is normally accomplished through its binding to gp160. The involvement of gp160 in the induction of CD4 degradation is restricted to its function as a CD4 trap, since, in the absence of Env, an ER retention mutant of CD4, as well as wild-type CD4 in cultures treated with brefeldin A, a drug that blocks transport of proteins from the ER, is degraded in the presence of Vpu.
614 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2025 | 4 |
| 2024 | 7 |
| 2023 | 9 |
| 2022 | 15 |
| 2021 | 18 |
| 2020 | 25 |