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

Abstract

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.

RICH2 is implicated in viraemic control of HIV-1 in black South African individuals

“…Tetherin (also called BST-2) is a type II transmembrane protein with a unique topology that allows it to tether enveloped viruses to the surface of infected cells, thereby restricting virus release, and in addition it is able to induce innate immune responses through the induction of cytokine/chemokine expression via the activation of NF-κβ (Galao et al, 2012); (reviewed (Mahauad-Fernandez and Okeoma, 2016)). Although HIV-1 can counteract the effect of tetherin through its Viral protein U (Vpu), the neutralizing activity by Vpu on tetherin does not appear to be absolute (Homann et al, 2011) suggesting that the balance of tetherin and Vpu may determine an individual’s ability to restrict viral dissemination, and thus may be a key molecule involved in the natural control of HIV-1.…”

Is tetherin a true antiviral: The influenza a virus controversy

“…Electron microscopic images have shown enveloped viruses tethered to the surface of infected cells via the GPI anchor of cell‐associated tetherin, thus, preventing the release of progeny virion . The restriction of virions at the cell surface by tetherin was subsequently described to elicit the host innate immune response through cytokine and chemokine induction . The unique ability of tetherin to act as an anchor, preventing the release of infectious progeny virion, contributes to the coining of its name, tetherin.…”

“…The unique ability of tetherin to act as an anchor, preventing the release of infectious progeny virion, contributes to the coining of its name, tetherin. In the past decade, tetherin has been believed to be an antiviral protein known to restrict the replication of a broad spectrum of enveloped viruses such as rhabdoviruses, togaviruses, orthomyxoviruses, flaviviruses, orthohepadnaviruses, retroviruses, arenaviruses, herpesviruses, filoviruses, and paramyxoviruses (see Table ) . Although the exact mechanism by which tetherin interacts with the progeny virion is unknown, it is speculated that the viral target is a ubiquitous protein located in the virion lipid envelope because of the ability of tetherin to restrict the budding of a vast range of envelope viruses …”

“…On the other hand, exogenously expressed tetherin often undergoes different post‐translational modifications resulting in the addition of high‐mannose carbohydrate moieties (predicted molecular weight: 28 000‐29 000 Da) . In general, tetherin has been reported to be involved in the inhibition of viral replication, cancer metastasis, regulatory T‐cell development, and regulation of autophagy . In this review, we aim at providing consolidated and up‐to‐date available information on the antiviral properties of tetherin, its modes of host cell tetherin counteraction, and the controversial reports on the role of tetherin in influenza A virus (IAV) life cycle.…”

IFN‐γ enhances the wound healing effect of late EPCs (LEPCs) via BST2‐mediated adhesion to endothelial cells

“…BST2 is a type 2 transmembrane protein with unique topology that enables its homophilic tethering . Through its ability to tether itself and signal, BST2 is known as a host immune response molecule to viral infection as well as cell adhesion . We investigated whether BST2 is involved in IFN‐γ effects on promoting LEPC adhesion to ECs and promoting angiogenesis.…”