BST2

Description

The BST2 (bone marrow stromal cell antigen 2) is a protein-coding gene located on chromosome 19.

Tetherin, also known as bone marrow stromal antigen 2, is a lipid raft associated protein that in humans is encoded by the BST2 gene. In addition, tetherin has been designated as CD317 (cluster of differentiation 317). This protein is constitutively expressed in mature B cells, plasma cells and plasmacytoid dendritic cells, and in many other cells, it is only expressed as a response to stimuli from IFN pathway.

== Gene activation == Tetherin is part of IFN-dependent antiviral response pathway. When the presence of virus and viral components is detected by recognition molecules such as (RIG-I), a cascades of interactions happen between signaling molecules, eventually the signal reaches the nucleus to upregulate the expression of interferon-stimulated genes (ISGs), this in turn activates IFN-α pathway to send the signal to neighboring cells, which causes upregulation in the expression of other ISGs and many viral restriction factors, such as tetherin. Tetherin/BST2 and BST1 genes are unregulated by the Nicotinamide (NAM) metabolism pathway.

== Function == Tetherin is a human cellular protein which inhibits retrovirus infection by preventing the diffusion of virus particles after budding from infected cells. Initially discovered as an inhibitor to HIV-1 infection in the absence of Vpu, tetherin has also been shown to inhibit the release of other RNA viruses such as the Lassa and Marburg virions suggesting a common mechanism that inhibits enveloped virus release without interaction with viral proteins. In addition, tetherin also restricts neuroinvasion of the DNA virus HSV-1. However, in contrast to its anti-viral role, it has recently been shown that basal levels of BST2 or Tetherin are required for HIV-1 replication but this isn't an indication that higher than basal levels of BST2 promotes viral replication.

BST2, also known as Tetherin, is an interferon (IFN)-induced antiviral protein that restricts the release of diverse enveloped viruses, including HIV-1, by tethering nascent virions to the membranes of infected cells. BST2 acts as a physical tether, preventing the spread of cell-free virions. BST2 can internalize tethered virions by endocytosis, leading to their degradation. Alternatively, tethered virions can remain on the cell surface. BST2 also plays a role in cell signaling, inhibiting cell growth and migration by suppressing MMP14 activity. It can also stimulate LILRA4/ILT7 signaling, providing negative feedback to IFN production by plasmacytoid dendritic cells. Additionally, BST2 is involved in the organization of the subapical actin cytoskeleton in polarized epithelial cells. BST2 exists in two isoforms, both of which restrict viral release. However, isoform 1 activates NF-kappa-B, while isoform 2 inhibits this activity and is resistant to Vpu-mediated degradation. BST2 forms homodimers and heterodimers, which are essential for its antiviral activity. It interacts with various proteins, including MMP14, LILRA4/ILT7, RNF115, and the Ebola GP protein.

BST2 is also known as CD317, HM1.24, TETHERIN.

Associated Diseases

WES Whole Exome Sequencing