Important progress in understanding the function of tetherin, known to have both anti-cancer and anti-viral properties, has been made by researchers at the University of Bristol.
Tetherin, a protein found in the body, prevents the release of mature HIV particles from infected cells by anchoring or 'tethering' the particles to the cell's surface. Tetherin also restricts the release of a wide range of different viruses, and has even been used as a target for drugs when treating lung tumours in mice.
Tetherin was only recently identified as forming part of the body's 'innate' immune system, the first line of defence against 'foreign bodies'. However, the cellular mechanism which accounts for the anti-viral and anti-tumour properties of tetherin remained a mystery until now.
Professor George Banting and colleagues in the University's Department of Biochemistry have found that tetherin performs a vital role in organising the internal 'skeleton' of epithelial cells which line many different structures and organs of the body, by providing a physical link with specialised regions on the cell surface, known as 'lipid rafts'. Their research was reported in the March issue of the Journal of Cell Biology.
Professor Banting said: "This is an important finding as lipid rafts have been implicated in a broad range of fundamental cellular processes, as well as playing a role in several human diseases e.g. Alzheimer's, Parkinson's, Prion, cardiovascular and autoimmune diseases.
"If tetherin does play a role in organising lipid rafts, this might partially explain how it combats the release of HIV particles from cells. A role for tetherin in organising lipid rafts might also help reconcile its association with such a diverse array of cellular processes".
Professor Banting and his team are now embarking on a new and exciting collaboration with Dr Oliver Keppler from the University of Heidelberg, Germany, who also works on tetherin, and its role in HIV infection.
They have recently shown that whilst tetherin anchors HIV particles to the surface of infected cells in humans, rats and mice, it is only the human version of tetherin that is targeted for degradation by a protein produced by the HIV virus. This protein, known as Vpu, comprises one of several ways by which the HIV virus counteracts the defence mechanisms of the immune system, allowing the virus to spread around the body. The paper reporting this work was published in the March issue of Cell Host and Microbe.
By joining forces, it is anticipated that the two research groups will be able to understand how the organisation of lipid rafts by tetherin relates to its numerous cellular functions, including those of the immune system. Ultimately, it is hoped that tetherin will provide a therapeutic target for a range of different viral infections, cancers, autoimmune and other diseases.
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