%0 Journal Article
%T Restriction of Retroviral Replication by Tetherin/BST-2
%A Jason Hammonds
%A Jaang-Jiun Wang
%A Paul Spearman
%J Molecular Biology International
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/424768
%X 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. 1. Introduction Viruses and their host organisms engage in a series of conflicts in which viruses can be thought of as leading the offense, placing the host on defense. Host defenses against retroviral replication have arisen in a wide variety of forms. Classical cellular and humoral immune responses may limit retroviral replication and may be sufficient to prevent adverse outcomes in some host-virus interactions. However, throughout the evolution of mammals a series of alternative host defense factors have arisen whose apparent primary function is to counteract retroviruses in ways that lie outside of classical innate or adaptive immunity. These intrinsic host defense mechanisms against viruses have come to light largely through comparative studies of inhibition or ˇ°restrictionˇ± of replication of HIV or SIV in cells from different origins and are collectively referred to as host restriction factors. APOBEC3G, TRIM5alpha, and tetherin are the most prominent of a series of host restriction factors to be identified in recent years that limit HIV replication. This paper focuses on the discovery and subsequent characterization of tetherin, with an emphasis on recent work aimed at elucidating how its structure leads to retention of particles on the plasma membrane and on how Vpu acts to overcome tetherin-mediated restriction. 2. Identification of Tetherin as an Antiviral Host Restriction Factor The discovery of tetherin is intimately linked to studies of the effects of the HIV accessory gene Vpu. Vpu is a small integral membrane protein encoded by HIV-1 and a limited subset of SIV species. Early studies
%U http://www.hindawi.com/journals/mbi/2012/424768/