BST-2/tetherin: Viral tether, viral sensor or both?

In the fields of virology and innate immunity, BST-2/tetherin is well known for its ability to block the egress of enveloped viruses from infected cells. This appears to be accomplished by 'tethering' virions to the cell surface, thereby limiting virion release. In the past year, several groups have discovered that BST-2/tetherin can activate NF-κB, a transcriptional activator that leads to the rapid expression of both proinflammatory cytokines and proteins involved in cell survival. While this new BST-2 function has been interpreted as a possible viral-sensing mechanism, there may also be broader implications for HIV gene regulation. This article reviews the evidence for BST-2-dependent NF-κB activation, and explores the significance of these exciting new results.