Tetherin
Ensembl |
| ||||||||
|---|---|---|---|---|---|---|---|---|---|
| UniProt |
| ||||||||
| RefSeq (mRNA) |
| ||||||||
| RefSeq (protein) |
| ||||||||
| Location (UCSC) | Chr 19: 17.4 – 17.41 Mb | n/a | |||||||
| PubMed search | [2] | n/a | |||||||
| View/Edit Human | |||
Tetherin, also known as bone marrow stromal antigen 2, is a lipid raft associated protein that in humans is encoded by the BST2 gene.[3][4][5] In addition, tetherin has been designated as CD317 (cluster of differentiation 317). This protein is constitutively expressed in mature B cells, plasma cells and plasmacytoid dendritic cells, and in many other cells, it is only expressed as a response to stimuli from IFN pathway.[6][7]
Gene activation
Tetherin is part of
IFN-dependent antiviral response pathway. When the presence of virus and viral components is detected by recognition molecules such as (RIG-I), a cascades of interactions happen between signaling molecules, eventually the signal reaches the nucleus to upregulate the expression of interferon-stimulated genes (ISGs), this in turn activates IFN-α pathway to send the signal to neighboring cells, which causes upregulation in the expression of other ISGs and many viral restriction factors, such as tetherin.[8][9][10]
Tetherin/BST2 and BST1 genes are unregulated by the Nicotinamide (NAM) metabolism pathway.[11]
Function
Tetherin is a human cellular protein which inhibits
Lassa and Marburg virions[12][13] suggesting a common mechanism that inhibits enveloped virus release without interaction with viral proteins. In addition, tetherin also restricts neuroinvasion of the DNA virus HSV-1.[14] However, in contrast to its anti-viral role, it has recently been shown that basal levels of BST2 or Tetherin are required for HIV-1 replication but this isn't an indication that higher than basal levels of BST2 promotes viral replication. More definite research is required.[15]
Structure
Tetherin is a
Vpu[18] which is thought to work by targeting tetherin for degradation via the β-TrCP2 dependent pathway.[19][20]
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. The stabilization of the protein through
disulfide bond within the coiled coil region seems to be important in its function[6]
Interaction with different viruses
Tetherin is known to block many different types of enveloped viruses by tethering the budding virus like particles (
ubiquitination and degradation of tetherin. It has been recently shown that tetherin gene variants are associated with HIV disease progression underscoring the role of BST-2 in HIV type 1 infection.[21] Another primate lentivirus, SIV, also, counteracts tetherin by their removal from the plasma membrane.[22][23] KSHV protein K5 also targets tetherin for degradation through ubiquitination.[24] Ebola counteracts tethrin through two mechanism. VP35 of Ebola, inhibits multiple steps of IFN-signaling pathway, which blocks the induction of tetherin as a downstream effect. Also, it has been noted that the full-length Ebola GP may either translocate tetherin or disrupt the structure of tetherin.[8] Sendai virus proteins HN and F direct tethrin to endosomes or proteasome for degradation.[25] CHIKV protein nsP1 interacts with tetherin by disrupting the tetherin-virion complex formation.[26]
Cell-to-cell transmission through
virological synapse.[6]
BST2/tetherin is a potent inhibitor of SARS-CoV-2.[27]
Tetherin as a biomarker and Other functions
Tetherin has been shown as a Type-I-IFN
HCMV), tetherin promotes entry of the virus, especially during cell differentiation. It has also been shown that tetherin is incorporated into newly formed virions.[30]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000130303 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 7607676.
- ^ "Entrez Gene: BST2 bone marrow stromal cell antigen 2".
- ^ PMID 17940069.
- ^ PMID 21994744.
- ^ PMID 31804007.
- ^ PMID 22958256.
- PMID 20485522.
- PMID 18200009.
- PMID 28515364.
- PMID 19091864.
- ^ Thaczuk D (2008-02-11). "Tetherin: a newly discovered host cell protein that inhibits HIV replication". NAM AIDS Map.
- PMID 26627457.
- PMID 34714669.
- PMID 19737401.
- ^ PMID 20688520.
- PMID 18200009.
- PMID 19730691.
- PMID 19837671.
- PMID 23148293.
- PMID 19436700.
- PMID 23043100.
- PMID 19605472.
- PMID 23468424.
- PMID 23411007.
- PMID 33024967.)
{{cite journal}}: CS1 maint: multiple names: authors list (link - PMID 23378022.
- PMID 23236425.
- PMID 22072961.
Further reading
- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. PMID 8125298.
- Furuya Y, Takasawa S, Yonekura H, Tanaka T, Takahara J, Okamoto H (November 1995). "Cloning of a cDNA encoding rat bone marrow stromal cell antigen 1 (BST-1) from the islets of Langerhans". Gene. 165 (2): 329–330. PMID 8522202.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. PMID 9373149.
- Ohtomo T, Sugamata Y, Ozaki Y, Ono K, Yoshimura Y, Kawai S, et al. (May 1999). "Molecular cloning and characterization of a surface antigen preferentially overexpressed on multiple myeloma cells". Biochemical and Biophysical Research Communications. 258 (3): 583–591. PMID 10329429.
- Vidal-Laliena M, Romero X, March S, Requena V, Petriz J, Engel P (2006). "Characterization of antibodies submitted to the B cell section of the 8th Human Leukocyte Differentiation Antigens Workshop by flow cytometry and immunohistochemistry". Cellular Immunology. 236 (1–2): 6–16. PMID 16157322.
- Elortza F, Mohammed S, Bunkenborg J, Foster LJ, Nühse TS, Brodbeck U, et al. (April 2006). "Modification-specific proteomics of plasma membrane proteins: identification and characterization of glycosylphosphatidylinositol-anchored proteins released upon phospholipase D treatment". Journal of Proteome Research. 5 (4): 935–943. PMID 16602701.
- Laplana M, Caruz A, Pineda JA, Puig T, Fibla J (February 2013). "Association of BST-2 gene variants with HIV disease progression underscores the role of BST-2 in HIV type 1 infection". The Journal of Infectious Diseases. 207 (3): 411–419. PMID 23148293.
External links
- BST2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.