Tetherin
Encyclopedia
Tetherin also known as bone marrow stromal antigen 2 is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the BST2 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

. In addition tetherin has been designated as CD317 (cluster of differentiation
Cluster of differentiation
The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules present on white blood cells, providing targets for immunophenotyping of cells...

 317).

Function

Tetherin is a human cellular protein which inhibits retrovirus
Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...

 infection by preventing the diffusion of virus particles after budding from infected cells. Initially discovered as an inhibitor to HIV-1 infection in the absence of Vpu
Vpu
Vpu is a HIV gene.Vpu stands for "Viral Protein U". Vpu is involved in viral budding, enhancing virion release from the cell by counteracting BST2 . In the absence of vpu, tetherin binds to the viral envelope and ties it to the cell membrane and other viral particles, impeding release of the viral...

, tetherin has also been shown to inhibit the release of other viruses such as the Lassa
Lassa fever
Lassa fever is an acute viral hemorrhagic fever caused by the Lassa virus and first described in 1969 in the town of Lassa, in Borno State, Nigeria, in the Yedseram river valley at the south end of Lake Chad. Clinical cases of the disease had been known for over a decade but had not been connected...

 and Marburg
Marburg virus
Marburg virus disease is the name for the human disease caused by any of the two marburgviruses Marburg virus and Ravn virus...

 virions. suggesting a common mechanism that inhibits enveloped virus release without interaction with viral proteins.

Structure

Tetherin is a type 2 integral membrane protein, with the N-terminus in the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...

, one membrane spanning domain, and a C-terminus modified by the addition of a glycosyl-phosphatidylinositol (gpi) anchor. When the virion buds from the surface of the cell, one of the tetherin membrane domains is in the new viral membrane, the other remains in the plasma membrane, tethering the virion to the cell. It is antagonized by the viral protein Vpu
Vpu
Vpu is a HIV gene.Vpu stands for "Viral Protein U". Vpu is involved in viral budding, enhancing virion release from the cell by counteracting BST2 . In the absence of vpu, tetherin binds to the viral envelope and ties it to the cell membrane and other viral particles, impeding release of the viral...

which is thought to work by targeting tetherin for degradation via the β-TrCP2 dependent pathway.

Tetherin exists as a dimer on the surface of cells, and prevention of dimerisation by mutating the cystine residues, prevents tetherin from inhibiting virus release, although it is still detectable in the cell.

External links

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