Restriction of Retroviral Replication by Tetherin/BST-2

Abstract

Tetherin/BST-2 is an important host restriction factor that limits the replication of HIV and other enveloped viruses. Tetherin is a type II membrane glycoprotein with a very unusual domain structure that allows it to engage budding virions and retain them on the plasma membrane of infected cells. Following the initial report identifying tetherin as the host cell factor targeted by the HIV-1 Vpu gene, knowledge of the molecular, structural, and cellular biology of tetherin has rapidly advanced. This paper summarizes the discovery and impact of tetherin biology on the HIV field, with a focus on recent advances in understanding its structure and function. The relevance of tetherin to replication and spread of other retroviruses is also reviewed. Tetherin is a unique host restriction factor that is likely to continue to provide new insights into host-virus interactions and illustrates well the varied ways by which host organisms defend against viral pathogens.

Figure 1

Schematic representation of tetherin domain structure. Tetherin is depicted as a parallel dimer with both transmembrane (TM) and glycophosphatidylinositol (GPI) membrane anchors in the same membrane. Disulfide linkages are depicted in green, and N-linked glycosylation sites pictured. CC: coiled coil; Y: tyrosine residues critical for endocytic motif.

Figure 2

(a) Tetherin on the cell surface of A3.01 T cells infected with NLUdel virus, treated with indinavir to preserve particle morphology for preparation. Arrows indicate immunogold beads; primary antibody was rabbit anti-tetherin polyclonal antisera. (b) Schematic depiction of parallel homodimers of tetherin retaining HIV particles on the plasma membrane; tetherin is not to scale in this diagram.