tetherin


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tetherin

A 29–33-kD type-II transmembrane glycoprotein encoded by BST2 on chromosome 19p131, which is expressed on some synovial cells, bone marrow stem cell lines, and type-I IFN-producing cells. It may be involved in sorting secreted proteins, and in pre-B-cell growth. It is an antiretroviral defense protein, blocking the release of enveloped virus from the cell surface. It is active against retroviruses, filoviruses, arenaviruses, and herpesviruses; is depleted upon HIV-1 infection by viral VPU protein via 20S proteasome degradation, and on infection by HHV-8 by ubiquitination and degradation. It may play a role in B-cell activation in rheumatoid arthritis.
 
Normal expression
Tetherin/BST2 is up-regulated on most cell types after stimulation with type-I IFNs and IFN-gamma, and is highly expressed on terminally differentiated dendritic cells.
 
Abnormal expression
Myeloma, renal cell carcinoma, melanoma cells.
References in periodicals archive ?
Bieniasz said that the finding helped to confirm that tetherin is capable of acting all on its own.
That's conceptually important, he said, because there is no specific interaction between tetherin and any viral protein, which makes it a more difficult problem for viruses to evolve resistance.
In the case of HIV, a protein called Vpu counteracts tetherin. They now show it does so by sequestering the host protein, which prevents its incorporation into the virus.
Bieniasz has suggested that the new insight into tetherin's and Vpu's modes of action, however, may lead to the development of Vpu blockers that could free up the innate host defense and inhibit HIV's spread.
He said that there is some possibility that tetherin exists in different forms that might explain differences among people in the progression of HIV or other viral infections.
However, the only common variation they've seen in the tetherin gene so far does not appear to affect its function.
"Tetherin is the first example of a protein that affects the virus replication cycle after the virus is fully made and prevents the virus from being able to go off and infect the next cell," he adds.
Known as one of the immune system's responses to a viral infection, tetherin stops the infected cell from releasing the newly made virus, thus shutting down spread to other cells.
However, the current study has revealed that the Ebola virus has developed a way to disable tetherin, thus blocking the body's response and allowing the virus to spread.
"This information gives us a new way to study how tetherin works.
Studies conducted in the past have shown that tetherin plays a role in the immune system's response to HIV-1, a retrovirus, and that it is also disabled by HIV.
"Because we see such broad classes of viruses that are affected by tetherin, it's possible that all enveloped viruses are targets of this antiviral system.