BST2

BST2, bone marrow stromal antigen 2, also known as tetherin or CD317, is a host cell membrane protein that restricts the release of enveloped viruses from infected cells. It is an interferon-inducible component of innate immunity and is expressed in several cell types, including plasmacytoid dendritic cells and B cells.

BST2 is a type II transmembrane protein featuring an N-terminal cytoplasmic tail, a single transmembrane helix, a long extracellular coiled-coil domain, and a GPI anchor at the C-terminus. It forms disulfide-linked homodimers and is glycosylated. The extracellular domain mediates dimerization, while the GPI-anchored tail and the transmembrane region enable the tethering of virions to the cell surface.

Mechanistically, BST2 tethers budding virions to the plasma membrane, preventing their release from the cell. Tethered virions may remain attached at the cell surface or be directed to endosomal pathways for degradation, thereby reducing the spread of infection.

BST2 expression is upregulated by type I interferons and other innate stimuli. It is constitutively expressed at varying levels across tissues and is particularly prominent on activated B cells and plasmacytoid dendritic cells, among others. The protein is subject to viral countermeasures; for example, HIV-1 Vpu downregulates BST2 from the cell surface, promoting virion release. Other enveloped viruses have evolved distinct antagonists as well.

In research and clinical contexts, BST2 serves as a marker for certain immune cell populations and as a focal point in studies of host antiviral defense. It is evolutionarily conserved among mammals and contributes to broader innate immune defense against enveloped viruses.